A Review of South African Traditional Medicinal Plants Used for Treating Fungal Coinfections in COVID-19 Patients with Respiratory Diseases

*Moleboheng Emily Binyane, Sitheni Samson Mashele and Polo-Ma-Abiele Hildah Mfengwana*

## **Abstract**

Fungal infections are still most prevalent in the South African population. Fungal respiratory infections and diseases are the cause of severe clinical challenges and mortality in patients with compromised immune systems. Clinical signs of coronavirus disease of 2019 (COVID-19) such as lung injury, hyperglycemia due to diabetes, host iron and zinc depletion, hypoxia, immunosuppression, steroid therapy, and longterm hospitalization predispose patients to opportunistic fungal infections. Fungal pathogens, including *Cryptococcus*, *Aspergillus*, and *Candida* species, cause coinfections in patients infected with (COVID-19), and this has a negative impact on the patients' pharmacological management goals. *Cryptococcus*, *Aspergillus*, and *Candida* species cause respiratory infections and illnesses including pneumonia, pulmonary aspergillosis, pulmonary candidiasis, and pulmonary cryptococcosis. South African traditional medicinal plants have been used in the treatment of respiratory symptoms and diseases caused by these fungal pathogens. Medicinal plants contain secondary metabolites possessing antifungal activity against *Cryptococcus*, *Aspergillus*, and *Candida* species. Moreover, medicinal plants are cheaper and easily accessible and are believed to be safe. This review documents the use of South African traditional medicinal plants including *Artemisia absinthium*, *Artemisia afra*, *Dicoma anomala*, *Felicia* species, *Mentha* species, *Ruta graveolens*, and *Seasia erosa* in the treatment of fungal infections and diseases caused by these pathogens.

**Keywords:** fungal coinfections, traditional medicinal plants, COVID-19, cryptococcosis, aspergillosis

## **1. Introduction**

Coronavirus disease of 2019 (COVID-19) patients with asymptomatic, mild, moderate, severe, and critical disease states are at risk of developing coinfection with pathogenic fungal species including *Aspergillus*, *Candida*, and *Cryptococcus* [1, 2]. Research reports suggest that COVID-19 predisposes patients to fungal, and other viral coinfections, and superinfections [3]. Concurrently occurring coinfections pose a massive challenge because it complicates diagnoses and COVID-19 management [3]. COVID-19 by severe acute respiratory coronavirus 2 (SARS-CoV-2) [1–4] causes respiratory symptoms such as shortness of breath, fever, fatigue, runny nose, headache, chest pain, congestion, anosmia, ageusia, sore throat, confusion, and vomiting [3, 5, 6], similar to those caused by *Aspergillus*, *Candida*, and *Cryptococcus* species infections [3]. An estimated 15% of COVID-19 patients admitted to the hospital's intensive care units (ICU) become coinfected by *Aspergillus* [7]. *Aspergillus* causes pulmonary aspergillosis including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), and invasive pulmonary aspergillosis (IPA) [8]. COVID-19-associated pulmonary aspergillosis (CAPA) is reported to have a 52% death rate [9]. *Aspergillus fumigatus/A. fumigatus* and *A. flavus* are the most common *Aspergillus* species causing coinfection in COVID-19 patients [4]. Conducted cohort studies on COVID-19-associated pulmonary aspergillosis have described its incidence to be between 2 and 33% [2, 10]. Aspergillosis is treated by the antifungal drug class, triazoles [1, 11], voriconazole, and isavuconazole being the first-line therapies [7, 9]. However, there are challenges associated with treatment therapy including the occurrence of azole-resistant *A. fumigatus* [11] and drug-drug interactions associated with the use of voriconazole, which lead to increased cardiotoxic effects of anti-SARS-CoV-2 agents [1]. The study conducted on COVID-19 patients who were severely and critically ill has revealed that dexamethasone is associated with increased pulmonary aspergillosis risk and death [12]. COVID-19-associated candidiasis (CAC) has occurred in various hospitals across countries [3]. CAC is an opportunistic infection caused by fungal species of *Candida* genus [3, 13]. Studies conducted in various countries, including the UK, Italy, Egypt, China, Iran, India, Gharbia, and Cairo, have revealed that *Candida* species including *C. albicans*, *C. tropicalis*, *C. glabrata*, *C. auris*, and *C. parapsilosis* are implicated in CAC [4, 13, 14]. Treatment of *Candida* infections includes azoles, echinocandin, Amphotericin B, and its liposomes [15]. However, there is an emergence of multidrug-resistant *Candida* species, including *C. glabrata*, *C. auris*, inherently resistant *C. krusei*, *C auris*-resistant fluconazole, and Amphotericin B, and fluconazole-resistant *C. parapsilosis* and *C. tropicalis* [4, 15]. Moreover, COVID-19 patients receiving treatment therapy, including tocilizumab, interferon type 1β, and lopinavir-ritonavir, are at an elevated risk of developing coinfections with *Candida* spp. [16]. Chloroquine, hydroxychloroquine, azithromycin, and protease inhibitors can cause direct myocardial toxicity, arrhythmias, and death [1]. COVID-19 patients coinfected with human immunodeficiency virus (HIV) or those with compromised immune systems are at risk of developing cryptococcosis [15]. The literature reveals a growing number of cryptococcosis cases in COVID-19 patients who were receiving corticosteroids and immunomodulators [17–19]. Pulmonary cryptococcosis is caused by two cryptococcal pathogenic species, namely *C. neoformans* and *C. gattii* [20, 21]. The recommended treatment therapy for cryptococcosis includes initial treatment with Amphotericin B in combination with flucytosine, followed by maintenance therapy with fluconazole [15, 22]. However, fluconazole-resistant *Cryptococcus* has been reported, and there is also an increased risk of antifungal toxicity [19]. Phytotherapy is an important solution for treating respiratory infections and diseases in adults and children [23]. Research reports that medicinal plants contain a variety of active secondary metabolites including alkaloids, saponins, and terpenoids with antifungal activity [24]. In South Africa

*A Review of South African Traditional Medicinal Plants Used for Treating Fungal Coinfections… DOI: http://dx.doi.org/10.5772/intechopen.112014*

(SA), the majority of people utilize traditional medicinal plants (TMPs) more than Western medicines because TMPs are cheaper, widely available, and considered to be more effective [25]. South African TMPs such as *Artemisia absinthium*, *Artemisia afra*, *Dicoma anomala, Felicia* species, *Mentha* species, *Ruta graveolens*, and *Searsia erosa* have been shown to possess antifungal activity against fungal pathogens, including *Cryptococcus*, *Aspergillus*, and *Candida* species [19, 26–29].

## **2. South African traditional medicinal plants used in the treatment of respiratory diseases caused by fungal pathogens**

### **2.1** *Artemisia* **species**

*Artemisia* is the most widely distributed genus belonging to the Asteraceae family [26, 27]. It consists of over 500 plant species of small herbs and shrubs, which are classified as annual, biennial, and perennial natural plants [27, 30]. These plants are used as traditional medicines [26]. Among all 500 *Artemisia* species, two species, *Artemisia afra* and *Artemisia absinthium* are the most used in SA [30]. *Artemisia afra* Jacq. ex Willd (**Figure 1**), also known as Wilde als in Afrikaans, African wormwood in English, Lengana in Sesotho, Umhlonyane in isiXhosa, and Mhlonyane in isiZulu, is a South African medicinal plant commonly used to treat respiratory symptoms and conditions such as bronchitis, asthma, colds, coughs, fever, pneumonia, sore throat, chills, whooping cough and headache [6, 19, 28, 30, 31]. *A. afra* is also used in combination with other TMPs such as *E. globulus* and *Lippia asperifolia* as prophylaxis for lung inflammation and to treat influenza [28]. The crude extract of *A. afra* has shown antifungal activity against *Candida albicans*, *Cryptococcus neoformans*, and *Aspergillus* species including *Aspergillus ochraceus*, *Aspergillus niger*, and *Aspergillus parasiticus* (**Table 1**) [19, 28, 32]. The leaves of *A. afra* contain numerous phenolic compounds with antimicrobial activity [33]. *A. afra* methanolic crude extract contains scopoletin, betulinic acid, and acacetin with good antimicrobial activity [34]. Other secondary metabolites including alkaloids, tannins, saponins, steroids, cardiac glycosides, and anthraquinones, are found in the crude extract and essential oil of *A. afra* [35]. Toxicity testing results of *A. afra* extract on McCoy fibroblast cell lines indicated moderate toxicity [19].

**Figure 1.** Artemisia afra*.*


*A Review of South African Traditional Medicinal Plants Used for Treating Fungal Coinfections… DOI: http://dx.doi.org/10.5772/intechopen.112014*


#### **Table 1.**

*Traditional medicinal plants used in respiratory diseases caused by fungal pathogens causing coinfections in COVID-19 patients.*

**Figure 2.** Artemisia absinthium*.*

**Figure 3.** Dicoma anomala*.*

*A. absinthium* (**Figure 2**), also known as Wormwood, Green ginger, Absinthium, or Absinthe in English, is used traditionally to treat fever [27, 29]. However, when used for a long period, *A. absinthium* is reported to be responsible for the central nervous system associated-adverse effects in patients such as convulsions, hallucination, and insomnia [27]. It contains secondary metabolites including lactones, terpenoids, flavonoid

glycosides, organic acids, tannins, and phenols [27]. Moreover, *A. absinthium* has antifungal activity against *C. albicans*, *A. niger*, and *A. flavus* (**Table 1**) [29]. *A. absinthium* is reported to be nontoxic when tested on Wistar Hannover rats for 13 weeks [77].

## **2.2** *Dicoma anomala*

*Dicoma anomala* (**Figure 3**) is a herbaceous plant belonging to the Asteraceae family of plants [36, 37]. It is known as Maagbitterwortel in Afrikaans, Fever bush in English, Hloenya in Sesotho, Inyongana in isiXhosa, and Isihlabamakhondlwane in isiZulu [36, 37]. In SA, *Dicoma anomala* is distributed in various provinces including the Free State, Limpopo, Gauteng, Northwest, Northern Cape, and Kwazulu natal [36, 38, 78]. Two subspecies, *Dicoma anomala* and *Dicoma gerrardi* are found in SA [37]. *Dicoma anomala* is used traditionally to treat respiratory symptoms and diseases including coughs, colds, and fever [36–38]. It has antifungal activity against *C. albicans*, and *A. niger* (**Table 1**) [36, 39]. *Dicoma anomala* produces bioactive compounds including phenolic acids, flavonoids, tannins, saponins, triterpenes, phytosterols, acetylenic compounds, sesquiterpene, lactones, and diterpene [40]. Results of acute and subchronic oral toxicity assessment of aqueous root extract of *Dicoma anomala* in rats for 14-day acute and 90-day subchronic toxicity testing have revealed that *Dicoma anomala* is not toxic at 0.5 to 2000 mg/kg [39]. *Dicoma anomala* dichloromethane: Methanol extract was found to be nontoxic at concentrations below 200 μg/ml when tested on Chang liver cells [79].

## **2.3** *Felicia muricata*

The genus *Felicia* consists of small shrubs of 85 known species of annual and perennial herbaceous plants [80]. *Felicia muricata* (**Figure 4**) is an aromatic herb belonging to the Asteraceae family [41, 42]. It is known as white *Felicia* in English and Ihbosisi or Ubosisi in isiXhosa [41–43]. *Felicia muricata* is widely distributed in SA, and in the Eastern Cape province, it is used traditionally to treat respiratory symptoms including headaches and fever [41, 43–45]. It has antifungal activity against *Aspergillus* species including *A. niger* and *A. flavus* (**Table 1**) [41]. *Felicia muricata* contains secondary metabolites including phenols, proanthocyanidins, flavonols, sesquiterpene lactones, triterpenoids, and flavonoids [41, 46]. The study conducted in Wistar rats using *Felicia muricata* aqueous leaf extract at 50, 100, and 200 mg/kg body weight for 14 days revealed that the plant is mildly toxic and safe for oral use, and requires further investigation [81].

**Figure 4.** Felicia muricata*.*

*A Review of South African Traditional Medicinal Plants Used for Treating Fungal Coinfections… DOI: http://dx.doi.org/10.5772/intechopen.112014*

## **2.4** *Mentha* **species**

Genus *Mentha* is a perennial and annual plant belonging to the Lamiaceae family [82, 83]. *Mentha spicata* (**Figure 5**) is also known as Spearmint, Brown mint, Garden mint, Lady's mint in English, and Imboza in isiXhosa [47]. It is a creeping rhizomatous and perennial herb cultivated in various tropical to temperate regions including SA [47]. *Mentha spicata* is used traditionally to treat respiratory symptoms and conditions such as asthma, flu, cold, and fever [48–50]. It has antifungal activity against *A. niger*, *Cryptococcus neoformans*, and *Candida albicans* (**Table 1**) [48, 51–53]. *Mentha* extracts and oils contain biopeptides responsible for their antifungal activity [54, 84]. *Mentha spicata* contains secondary metabolites including flavonoids, tannins, sterols, polyphenols, sterols, triterpenes, and glycosides [53]. Toxicity investigational study of *Mentha spicata* methanolic extract in mice using 500, 1000, 2000, and 5000 mg/ kg for 24 hours to 14 days revealed that the plant is safe for oral administration [53]. *Mentha longifolia* (**Figure 6**), also known as Wild mint, Silver mint, and Horsemint in English, Koena in Sesotho, Inxina, and Inzinziniba in isiXhosa, is naturally present

**Figure 5.** Mentha spicata*.*

**Figure 6.** Mentha longifolia*.*

in SA [49, 55–59]. It is traditionally used to treat respiratory conditions including the common cold, cough, sore throat, headache, flu, and fever [60, 61]. *Mentha longifolia* has antifungal activity against *Candida albicans*, *Candida glabrata*, *A. flavus*, *A. fumigatus*, and *A. niger* (**Table 1**) [55, 57, 62]. The essential oil of *Mentha longifolia* contains a terpenoid and methanol, that has fungistatic and fungicidal activities [85]. *Mentha longifolia* possesses other secondary metabolites such as flavonoids, ceramides, cinnamates, ester, ketones, monoterpenes, phenols, polyene, and sesquiterpenes [60]. A toxicity testing study of *Mentha longifolia* methanolic extract in rats revealed that the acute oral dose was nontoxic [86].

## **2.5** *Ruta graveolens*

*Ruta graveolens* (**Figure 7**) belongs to the *Rutaceae* family [63]. It is commonly known as Ruta, Rue, Garden rue, and Herb of grace in English, and Wynruit in Afrikaans [63–66]. *Ruta graveolens* is distributed worldwide including in SA [64, 66]. It is used traditionally to treat respiratory symptoms and diseases including fever, headache, colds, and influenza [64, 66]. *Ruta graveolens* has antifungal activity against *Candida albicans*, *Candida tropicalis*, *Candida parapsilosis*, *Candida glabrata*, *Aspergillus flavus*, *Aspergillus fumigatus*, and *Cryptococcus neoformans* (**Table 1**) [67– 70]. The essential oil of *Ruta graveolens* contains ketones responsible for antimicrobial activity [67]. *Ruta graveolens* is rich in bioactive compounds including coumarins, coumarin dimers, dihydrofuranocoumarins, quinolone, furoquinoline, dihydrofuroquinoline, phenolic acids, alkaloids, and flavonoids [71]. Toxicity investigation of *Ruta graveolens* in Wistar rats has shown that the plant's seeds extract at 50 mg/kg/day was not toxic after oral administration for 4 weeks [87].

## **2.6** *Seasia* **species**

The genus *Searsia* (previously known as *Rhus*) belongs to the family *Anacardiaceae*. It is widely distributed in tropics and subtropics areas globally mostly in the African continent, especially southern Africa [88, 89]. Most *Searsia* species such as *Searsia* 

**Figure 7.** Ruta graveolens*.*

## *A Review of South African Traditional Medicinal Plants Used for Treating Fungal Coinfections… DOI: http://dx.doi.org/10.5772/intechopen.112014*

*erosa*, *Searsia divaricate*, *Searsia lancea*, *Searcia natalensis*, and *Searsia undulata* are traditionally used to treat respiratory illnesses including colds, influenza, and microbial infections [68, 90]. *Searsia* species have pharmacological activities including anti-inflammatory, anticancer, antiviral, antimalarial, antidiarrheal, and antioxidant activities [91]. *Searsia erosa* (**Figure 8**), also known as Broom karee, Besembos in English, and Tśilabele in Sesotho [68, 72, 73], is used traditionally to treat respiratory diseases including colds [72, 73]. It has antifungal activity against *Cryptococcus* 

**Figure 8.** Searsia erosa*.*

**Figure 9.** Searsia lancea*.*

**Figure 10.** Searsia natalensis*.*

*neoformans* (**Table 1**) [74]. Aqueous extracts of *Searsia erosa* were found to be nontoxic when tested using the brine shrimp lethality assay [74]*. Searsia lancea* (**Figure 9**) also known as African sumuc, and Willow rhus in English is used to treat colds and influenza [68]. It contains bioactive compounds including flavonoids, tannins, and phenols [75]. *Searsia lancea* has antifungal activity against *A. flavus* (**Table 1**) [76]. *Searsia natalensis* (**Figure 10**), also known as Natal rhus in English is used to treat influenza [76], possesses secondary metabolites including epicatechin, 3β-sitosterol, 3β-sitosterol, glucoside stigmasterol, lupeol [75]. *Searsia natalensis* has antifungal activity against *C. albicans* and *A. Niger* [75]. There are no studies documenting the toxicity analysis of reported *Searsia* species, and further studies are warranted to determine the safety of these medicinal plants.

**Table 1** shows the traditional use of South African TMPs in respiratory conditions including, asthma, bronchitis, colds, coughs, sore throat, headaches, lung inflammation, influenza, chills, whooping cough, pneumonia, and fever [6, 19, 28–31, 63, 70, 85]. These TMPs are also reported to possess antifungal activity against *Aspergillus*, *Candida*, and *Cryptococcus* species, which are implicated in coinfections with COVID-19.

## **3. Conclusions**

This review has summarized TMPs commonly used in the treatment of respiratory diseases caused by fungal pathogens such as *Aspergillus*, *Candida,* and *Cryptococcus* species implicated in coinfection in COVID-19 patients. *Artemisia absinthium*, *Artemisia afra*, *Dicoma anomala*, *Felicia* species, *Mentha* species, *Ruta graveolens*, and *Searsia erosa* have been used in SA for the treatment of respiratory symptoms and diseases including asthma, bronchitis, colds, coughs, sore throat, headaches, lung inflammation, influenza, chills, whooping cough, pneumonia, fever, and flu. These TMPs contain secondary metabolites responsible for their antifungal activities. *In vitro* and *in vivo* toxicity studies have confirmed that these TMPs are nontoxic for oral administration. However, further testing using animal models and clinical studies are required to profile the pharmacokinetics and pharmacodynamics of these TMPs before recommendations to use in coinfections in COVID-19 patients.

*A Review of South African Traditional Medicinal Plants Used for Treating Fungal Coinfections… DOI: http://dx.doi.org/10.5772/intechopen.112014*

## **Acknowledgements**

We acknowledge the Central University of Technology, Department of Health Sciences and Walter Sisulu University, Department of Internal Medicine and Pharmacology, and National Research Foundation (Black Academics Advancement Programme).

## **Conflict of interest**

The authors declare no conflict of interest.

## **Author details**

Moleboheng Emily Binyane1 , Sitheni Samson Mashele2 and Polo-Ma-Abiele Hildah Mfengwana2 \*

1 Faculty of Health Sciences, Department of Internal Medicine and Pharmacology, Walter Sisulu University, Mthatha, South Africa

2 Faculty of Health and Environmental Sciences, Department of Health Sciences, Central University of Technology, Bloemfontein, South Africa

\*Address all correspondence to: pntsoeli@cut.ac.za

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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## **Chapter 12**

## Immunomodulatory Plant Based Foods, It's Chemical, Biochemical and Pharmacological Approaches

*Bamidele Sekinat Olayem, Origbemisoye Babawande Olaitan and Akinbode Badiu Akinola*

## **Abstract**

There has been a growing interest in research focused on enhancing immune function, given its crucial role in maintaining human health and preventing illnesses. While antibiotics are commonly employed in clinical settings to treat and prevent various diseases, their synthetic nature often leads to undesirable side effects. Since the beginning of time, medicinal plants have been employed in healthcare. Global research has been done to confirm their efficacy, and some of the results have sparked the development of plant-based medications; also, plant-based diets have emerged as leading contenders in the field of chronic disease prevention. They offer affordability, natural origins, and easy accessibility. One key reason for their effectiveness is their Immunomodulatory effect, whereby they stimulate immune cells and influence the development of immune molecules. This comprehensive review aims to explore the potential of medicinal plant as well as plant-based foods while examining their medicinal properties and their utilization in preventing and managing disease through their chemicals, biochemical components, and pharmacological approaches.

**Keywords:** medicinal plant, plant-based foods, bioactive components, immune system, diseases

## **1. Introduction**

The use of plants as a primary source of medicines can be traced back to early civilizations of the world. They are natural and less expensive products, which are becoming more and more popular for both preventative and therapeutic purposes as a result of the negative side effects of continuous use of conventional medications [1]. Several plants are known to have natural healing capabilities for a variety of diseases due to their high contain of bioactive substance. These properties have contributed significantly to the development of modern medicine. Researchers have successfully assisted in identifying the potencies of these plants to cure diseases, thanks to generations' worth of knowledge [2–4]. These insights have helped to understand the various uses of different medicinal plants in different cultures around the world. Also, functional meals derived from plants have been demonstrated to

have immunomodulatory effects due to the presence of bioactive components that have been utilized to elucidate the biological and chemical activities in the human body system, and these have developed as a new trend. According to Origbemisoye and Bamidele [5] reports, utilizing these immunostimulatory foods and herbs can strengthen the immune system and safeguard the body against COVD-19 and any other ailments.

Immune dysfunction has been exacerbated by stress and unhealthy lifestyle choices, which has increased demand for functional and nutraceutical foods. Depending on how they perform, the bioactive elements in foods made from plants and herbs are divided into primary and secondary metabolites. Protein, carbohydrates, lipids, and nucleic acids are primary metabolites that the body uses to support, grow, and maintain daily functions. Secondary metabolites, on the other hand, have biological properties like antioxidant activity, antimicrobial activity, enzyme detoxification regulation, immune system modulation, reduced platelet aggregation, hormone metabolism, and anticancer property [6], which are frequently attributed to their high concentration of phenolic chemicals, flavonoids, curcumin, saponin, glucosides, lignans, phenolic acids, alkaloids, terpenes, and steroid [6] that are typically found in medicinal plants, foods, and ingredients eaten every day, such as legumes, cereals, fruits and vegetables, herbs, spices, and essential oils [7]. This study reviews the bioactive compound in medicinal plants and functional plant-based foods that exhibit immunomodulatory effects as well as their chemical, biochemical, and pharmacological approaches.

## **2. Medicinal plants, their bioactive components, and pharmacology approach**

## **2.1 Plant and herbs**

There are several phytochemicals with important qualities found in all kinds of plants. Several antioxidant compounds that are present in naturally occurring plant sources and function as active oxygen or free radical scavengers are included in the comprehensive antioxidative defense mechanism that plants have developed, according to Youwei et al. [8]. Plants are a potential source of new compounds with antioxidant activity since they produce a lot of antioxidants to counteract oxidative stress. As a result, dietary antioxidants have lately generated more research interest. A lower frequency of illnesses brought on by oxidative stress from free radicals has been associated with dietary antioxidant intake from plant materials [9].

## *2.1.1 Phyllanthus niruri (stone breaker)*

It is a native of the Amazon rainforest and other tropical nations like India, China, the Bahamas, and the Philippines [10, 11]. It is a widely used plant that is said to have anticancer, anticarcinogenic, hypolipidaemic, hepatoprotective, antiviral, antihypertension, and antidiabetic qualities. *P. niruri* contains a number of bioactive compounds, including lignin, phyllanthin, hypophyllanthin, flavonoids, glycosides, and tannins [12]. All of the plant's components, including the fruits and leaves, are employed in the medicinal formulations.

Phyllanthin, a bitter component of lignans, and hypophyllanthin, a non-bitter component, were isolated from *P. niruri* [13]; these lignans are significant because

### *Immunomodulatory Plant Based Foods, It's Chemical, Biochemical and Pharmacological… DOI: http://dx.doi.org/10.5772/intechopen.112406*

of their wide range of therapeutic properties, including hepatoprotection, antitumor, antimitotic, and antiviral properties [14–17] as well as antioxidant activities. According to reports, leaves contain the highest concentrations of phyllanthin (0.7% w/w) and hypophyllanthin (0.3% w/w), whereas the stem contains only trace amounts of both [18]. Other lignans with significant therapeutic potentials are reported in *Phyllanthus amarus* including niranthin, phyltetralin, nirtetralin, isonirtetralin, hinokinin, lintetralin, isolintetralin, demethylenedioxy-niranthin, 5-demethoxy-niranthin, and so on.

Flavonoids are polyphenolic substances that belong to the class of secondary metabolites found in plants. The many categories include catechins, chalcones, favanone, favones, favonols, isofavones, and their derivatives. The many bioactivities of *P. niruri* are also owed to this family of chemicals. The main flavonoids found in the plantincludes rutin, astragalin, kaempferol, quercetin, and so on, which contribute to the herb's antioxidant properties. With a wide variety of structural types, biosynthesis processes, and pharmacological effects, alkaloids are among the most diverse categories of secondary metabolites; a wide variety of structural types, biosynthesis processes, and pharmacological actions were discovered. Alkaloids are cyclic nitrogenous chemicals with a low molecular weight. The *Angiospermae*, or flowering plants, are the main source of alkaloids; they contain roughly 20% of them. Since ancient times, their broad variety of pharmacological properties, notably in mammals like humans, have drawn attention, in addition to their role in plant defense against herbivores and pathogens. Among their broad class of secondary metabolites, *P. niruri* is also known to contain a number of alkaloids, such as securinine, epibubbialine, and isobubbialine, which are also accountable for the herb's many supported therapeutic effects.

#### *2.1.2 Garcinia kola (bitter Kola)*

A species of flowering plant known as *G. kola* is a member of the *Clusiaceae* or *Guttiferae* family of tropical plants. It is a domesticated giant forest tree that is highly prized for its palatable nuts throughout most of West and Central Africa. It is a plant that has long been valued for both its medicinal and nutritive properties. The seeds offer potential therapeutic effects due to the concentration of the flavonoid and other bioactive components, and they are also employed in folk medicine in many herbal preparations [19, 20]. All of this plant's parts, including the nut, leaf, stem, bark, and root, have been discussed in several ethnobotanical and pharmacological studies, albeit the nut is still the one that is most frequently employed.

Flavonoids predominate among the phytochemical components of *G. kola* seeds, which also include proteins, glycosides, reducing sugar, starch, sterols, and triterpenoids, according to Esimone et al. [21]. Other chemical analyses of the seeds have revealed that they contain a complex mixture of phenolic compounds, including GB-type biflavonoids; xanthones; benzophenones; cycloartenol; triterpenes [22, 23]; kolaviron [23, 24]; the chromanols, garcioic and garcinal [25]; biflavonoids; xanthones; kolanone; ameakoflavone; 2,4,3-methylenecyclartenol; coumarine; prenylate benzophenones [26]; and oleoresin [27]. Traditional African medicine makes considerable use of extracts from *G. kola* [28, 29] particularly when creating treatments for laryngitis, coughing, and liver conditions [30]. As a purgative, antiparasitic, antimicrobial, antiviral, and anti-inflammatory; antidote to the effects of *Strophanthus gratus*; and remedy for guinea-worm infection and for gastroenteritis, rheumatism, asthma, menstrual cramps, throat infections, headache relief, colic relief, chest colds, cough, and liver disorders are just a few of its additional medical uses [31, 32].

#### *2.1.3 Aloe vera*

Aloe vera, often referred to as the "miraculous plant" or "wonder plant," has been utilized for medicinal purposes by various cultures for over 3000 years [33]. In the Democratic Republic of the Congo, aloe vera has been traditionally employed as a botanical medicine to treat illnesses and has shown significant potential against COVID-19. It is also known for its soothing properties and has been traditionally used for various health purposes. It has been reported to exhibit antiviral activity against certain viruses, including herpes simplex virus and influenza virus. Additionally, aloe vera has been shown to possess immunomodulatory effects by enhancing immune responses and stimulating the production of cytokines. Experimental studies have revealed that aloe vera exhibits potent virucidal properties with a broad spectrum of action. Notably, the toxicity of these plant extracts has been demonstrated to be benign both in vitro and in vivo. Aloe vera contains various antiviral compounds, including anthraquinones, which function independently or in conjunction with pharmaceutical targets such as the SARSCov-2 protease 3CLPro. These antiviral properties complement the plant's inherent anti-inflammatory and immunomodulatory capabilities [34]. It is plausible that a phytodrug based on aloe vera extracts could attenuate the expression of pro-inflammatory factors and receptors associated with acute respiratory distress, the primary cause of COVID-19 mortality, while simultaneously weakening the immune system. Consequently, aloe vera and its key secondary metabolites may play a crucial role in the treatment of COVID-19 and cardiovascular diseases, especially when combined with viral protease inhibitors, which represent the optimal therapeutic choice [5].

## *2.1.4 Stinging nettle (Urtica dioica)*

Stinging nettle (*U. dioica*) has a long history of use in traditional medicine across various nations. It is believed to offer therapeutic benefits for the nervous, immune, cardiovascular, and digestive systems [35]. Previous reports have indicated that specific lectins, such as the agglutinin lectin from *U. dioica* (UDA), the agglutinin lectin from leeks (Allium porrum Agglutinin or APA), and the NICTABA lectin from tobacco (*Nicotiana tabacum*), isolated from the rhizomes of *U. dioica*, have shown the strongest inhibition against the proliferation of the Covid-19 virus, with an EC50 (50% effective concentration) of 1.3 g/ml in in vitro studies. These pure extracts exhibited low toxicity [36]. Furthermore, UDA has demonstrated inhibitory effects on the SARS-CoV virus in in vitro studies [37].

### *2.1.5 Torreya nucifera (nutmeg-yew from Japan)*

The Taxaceae tree *T. nucifera* has a history of use in traditional Asian medicine for the treatment of stomachaches, hemorrhoids, and rheumatoid arthritis [38]. This tree is found in snowy regions near the sea of Jeju Island in Korea. It has been investigated as a potential inhibitor of SARS-CoV 3CLpro. Ethanol extracts of *T. nucifera* leaves were obtained and evaluated for their inhibitory activity against SARS-CoV 3CLpro using a fluorescence resonance energy transfer (FRET) technique. The leaves' ethanol extracts yielded 12 phytochemicals with inhibitory activity against SARS-CoV 3CLpro, including eight diterpenoids and four biflavonoids. The findings suggest the potential of *T. nucifera* as a source of natural compounds with inhibitory effects on SARS-CoV 3CLpro.

*Immunomodulatory Plant Based Foods, It's Chemical, Biochemical and Pharmacological… DOI: http://dx.doi.org/10.5772/intechopen.112406*

### *2.1.6 Alder bark*

Alder bark is known to contain salicin, an anti-inflammatory compound that is converted into salicylic acid in the body. It also contains diarylheptanoids, a type of secondary metabolite [39]. Red alder bark (*Alnus rubra*) has been traditionally used in several Native American cultures to treat conditions such as poison ivy, bug bites, and skin irritations. The Blackfeet tribe, in particular, has utilized an infusion made from red alder bark to treat tuberculosis and lymphatic ailments. In a study by Park et al. [40], the inhibitory potential of nine diarylheptanoid derivatives (platyphyllenone, hirsutenone, platyphyllone, platyphyllonol-5-xylopyranoside, hirsutanonol, oregonin, rubranol, rubranoside B, and rubranoside A) isolated from *Alnus japonica* Steud (Betulaceae) of Korean origin was investigated. The study evaluated the inhibitory effects of these compounds against both SARS-CoV 3CLpro and PLpro using a continuous fluorometric assay.

## *2.1.7 Licorice root*

Licorice (*Glycyrrhiza glabra*) root contains a major component called glycyrrhizin [41, 42]. This compound has a long history of traditional use for the treatment of gastritis, bronchitis, and jaundice. It is known to possess antioxidant and anti-inflammatory properties and has been reported to stimulate the production of interferons in the body [43]. Glycyrrhizin has been shown to inhibit the attachment of SARS-CoV to cells, particularly during the initial phase of the virus infection cycle [44]. Licorice root also contains flavonoids, glycyrrhetinic acid, β-sitosterol, and hydroxyl coumarins [43]. Cinatl et al. [45] demonstrated the anti-SARS-CoV activity of glycyrrhizin, and later, Pilcher [44] suggested licorice and glycyrrhizin as potential candidates for the development of drugs against SARS-CoV. However, it should be noted that the development of a commercial drug for SARS-CoV is still a long process. Further research by Chen et al. [46] confirmed the anti-SARS-CoV properties of glycyrrhizin, and numerous review articles have been published highlighting its positive antiviral activity [47–49].

## **2.2 Plant-based functional foods and their pharmacology uses**

## *2.2.1 Legumes*

Legumes, a member of the *Fabaceae* family, are dried seeds that have been consumed by humans for over 10,000 years. They are primarily cultivated for human consumption and include popular varieties such as soybeans, peanuts, lentils, lupins, alfalfa, beans, tamarind, and clovers. Legumes have been utilized to prevent and manage diet-related diseases such as metabolic disorders, inflammatory bowel disease, diabetes, and cardiovascular disease, primarily due to the presence of bioactive components with immunomodulatory properties [50]. Flavonoids are abundant in legumes, and various phenolic acids, including p-hydroxybenzoic, protocatechuic, syringic, gallic, vanillic, caffeic, and sinapic acids, have been identified [51, 52]. Phenolic acids commonly found in legumes include trans-ferulic acid, trans-pcoumaric acid, and syringic acid, with navy bean, lima bean, and cowpea exhibiting the highest concentrations, respectively [51]. Flavonoids in legumes exist in the form of glycosides or aglycones. Chemically, flavonoids are a class of phenolic compounds with a C6-C3-C6 skeleton [53]. Their structure provides hydroxyl groups in the

B-ring, enabling the stabilization of radicals by supplying hydrogen and electrons to hydroxyl, peroxyl, and peroxynitrile radicals [54].

As a result, stable flavonoid radicals are generated, and flavonoids can be classified into various classes based on the position of the B ring and the replacement pattern of the C ring. Flavonols, flavanones, isoflavones, anthocyanidins, and flavones are among the flavonoids found in legumes [55–57]. The consumption of pulses has been suggested to reduce the risk of cancer according to the World Cancer Research Fund/ American Institute for Cancer Research (WCRF/AICR) 2010 report [58]. Several research studies have investigated the effects of commonly consumed legumes on cancer cell proliferation [59–62]. The high fiber content of pulses has been associated with a reduced risk of colon cancer. Fiber from common beans has been shown to have an antiproliferative effect and induce apoptosis in colon cancer cells [63, 64]. The mineral composition of pulses, including zinc and selenium, which reduce oxidative stress and inhibit tumor cell growth, may also contribute to their anticancer properties [65, 66]. The anticancer effects of pulses are attributed to biologically active components such as tannins, phytic acid, saponins, and protease inhibitors [67, 68]. Saponins, for example, have been found to inhibit the growth of leukemia, colon, lung, and other cancer cells [69, 70]. Protease inhibitors exert an anticancer effect by reducing the rate at which cancer cells divide and by blocking tumors from secreting proteases that could otherwise kill nearby cells [71].

Both pinto bean trypsin inhibitor [65] and pea protease inhibitor [55] have demonstrated in vitro anti proliferative effects. The phytochemicals' anticancer effects could be attributed to their phytoestrogenic characteristics [66]. For instance, daidzin and genistin found in soybeans exhibit this effect by binding to the human estrogen receptor [67]. Hormonal imbalance is implicated in several hormone-dependent malignancies such as breast and prostate cancer. Soybean isoflavones, which resemble mammalian estrogen, have been shown to have protective effects against hormonedependent cancers by binding to the human estrogen receptor in both agonistic and antagonistic manners, thus exhibiting beneficial effects on hormone-dependent tumors [66].

Evidence from numerous epidemiological studies has demonstrated a link between pulse consumption and a decrease in cardiovascular diseases (CVDs) [67]. Pulses have an impact on various factors related to CVDs, including lipid profiles, blood pressure, and inflammation [64]. Consuming legumes has been shown to reduce LDL-C and total cholesterol levels [68, 69]. The mono- and polyunsaturated fatty acids and sterol content in pulses contribute to increased levels of HDL cholesterol while decreasing total and LDL cholesterol [70–72]. The association between pulse consumption and lower levels of total and LDL cholesterol has been demonstrated in clinical trials and meta-analyses [73–75]. Isoflavones in pulses also play a crucial role in the treatment of CVDs through their antihypertensive, anti-atherosclerotic, and antiplatelet activities [76]. When consumed in high amounts, the isoflavones found in kidney and black beans stimulate adipocytes to produce adiponectin, a cardioprotective hormone that exhibits anti-inflammatory effects on blood vessel cells and is associated with a lower risk of heart attack [64, 77, 78]. There is an inverse relationship between pulse consumption and blood pressure [79]. Randomized clinical studies and meta-analyses have shown that diets high in pulses can lower systolic and mean arterial blood pressure [80–82].

Diabetic patients have also shown a decrease in blood pressure and heart rate [80, 83, 84]. Pulses are often chosen as a meal by diabetics due to their high fiber content and potential benefits for glycemic management [85–87]. Increased

### *Immunomodulatory Plant Based Foods, It's Chemical, Biochemical and Pharmacological… DOI: http://dx.doi.org/10.5772/intechopen.112406*

consumption of beans in the diet may help with glycemic management and lower the risk of diabetes [88]. Randomized controlled trials (RCTs) and epidemiological research have demonstrated that pulses reduce fasting insulin and blood glucose levels, as well as fructosamine and glycosylated hemoglobin when combined with low glycemic index (GI) and high fiber diets [89–91]. The polyphenols present in legumes are also associated with regulating the absorption of carbohydrates in the intestine. Polyphenols such as diadzein, caffeic acid, ferulic acid, syringic acid, naringenin, and kaempferol inhibit the pancreatic enzymes alpha-amylase and alpha-glucosidase, which are responsible for breaking down starch in the intestine, thereby lowering blood sugar levels [92]. Furthermore, the antioxidant properties of polyphenols protect against oxidative stress generated by hyperglycemia-related free radical production. Mungbean flour, for example, has a low glycemic index and is rich in fiber [93].

The low glycemic index of mungbeans indicates that consuming them can help prevent diabetes. Soybeans, especially, have a low glycemic index and are an important component in the diet of diabetics. Legumes, particularly soybeans, are the main source of isoflavones, which have estrogenic activity. Adding isoflavones like genistein, daidzein, and glycosides to the diet may help prevent osteoporosis. Experimental investigations have shown that isoflavones work in various ways, including promoting osteoblast activity and proliferation to preserve bone mass against the action of osteoclast cells, which break down bone [94]. Research by Frassetto et al. [95] found an inverse relationship between plant protein intake and hip fracture occurrence, indicating that plant protein intake, including from legumes, is beneficial for bone health. Meals consisting of lentils, chickpeas, and yellow peas have been found to be more satisfying and effective at reducing hunger compared to a breakfast of cereals, vegetables, and cheese [90, 96]. Pulses may help manage appetite and limit calorie intake in diets. Epidemiological data also suggests a favorable relationship between bean consumption and body weight [79]. Greater weight loss was observed with a diet including four servings of pulses per week for 8 weeks within a 30% energy-restricted diet compared to an energy-restricted diet that excluded pulses [73]. Reduction in body weight has been reported after 3 months with a high-pulse-low-GI diet [97]. Although significant weight reduction was not observed in other trials of pulse-rich diets over a period of 6–18 months, a reduction in waist circumference was observed [98]. Consuming pulses has been associated with potential benefits for longevity and overall health [64]. A study by Darmadi-Blackberry et al. [99] found that elderly people who consume a lot of legumes exhibit persistent and significant protective effects. Additionally, frequent bean consumption in older adults has been associated with reduced stress, anxiety, and depression [100].

### *2.2.2 Cereals*

Cereals, such as wheat and rice, have been recognized as functional foods and nutraceuticals due to their high protein, dietary fiber, and bioactive component content, which contribute to antioxidant and anti-inflammatory activities. These properties make cereals beneficial in preventing diseases associated with metabolic syndromes, including obesity, cardiovascular disease, and type 2 diabetes [101, 102]. Cereals like wheat, sorghum, barley, millet, and rice have been found to possess antihypertensive and antioxidant activities, which help regulate hormonal control processes, lower blood pressure, and mitigate other noncommunicable disorders [103–106].

#### *2.2.2.1 Rice (Zizania spp.)*

Rice (*Zizania* spp.) contains phenolic acids, flavonoids, and phytochemicals with antioxidant capabilities that contribute to the prevention of chronic diseases [107, 108]. Rice consumption has been associated with lower rates of chronic diseases, likely due to the presence of phytochemical antioxidants [109]. Wild rice (*Zizania latifolia*) has been shown to have antihypertensive effects, attributed to its polyphenol content, particularly quercetin, which has demonstrated blood pressure-lowering and protective effects against cardiovascular diseases [110]. Research on virgin rice bran oil has also demonstrated its potential in preventing hypertension induced by L-N-G nitroarginine methyl ester (L-name) in rats, improving hemodynamic changes and reducing oxidative stress and vascular inflammation [111]. Rice bran is rich in biologically active substances that benefit human health, supporting immune, antioxidant, anticancer, and antidiabetic functions [112]. Rice's anti-inflammatory, anti-allergy, anti-atherosclerosis, anti-influenza, anti-obesity, and antitumor properties contribute to defense against various chronic and degenerative diseases, including hypertension, and may play a role in preventing COVID-19 infection.

#### *2.2.2.2 Wheat (Triticum spp.)*

Wheat (*Triticum* spp.) is a crucial staple food, providing a significant portion of starch and calories in meals. Studies have shown that regular consumption of wheat, particularly dietary fiber and other bioactive substances, are associated with a decrease in chronic diseases [113]. Wheat contains various phytochemicals, including phenolic acids, terpenoids, tocopherols, and sterols, with whole wheat containing significant amounts of phenolic acids [114, 115]. The processing and utilization of wheat significantly impact the composition of bioactive compounds and, consequently, the health benefits, such as improvements in colon functions, cancer prevention, protection against obesity, weight loss promotion, and other positive effects [116–125].

Research on wheat's pharmacology has identified ACE-inhibitory peptides derived from wheat gluten protein hydrolysates, which have potential cardiovascular benefits [126]. Structure plays a role in the inhibitory activity of these peptides, and certain sequences with specific amino acids exhibit greater inhibitory activity toward ACE [127]. The isolation of phenols from protein fractions in wheat flour has been found to enhance antihypertensive activity and antioxidant characteristics while reducing allergenicity [128]. Polysaccharides found in wheat have also shown the ability to boost the immune response to infectious diseases by activating protein pathways in cells like macrophages, thereby stimulating immune response control processes [129].

#### *2.2.2.3 Millet*

Millet is made up of several species that are not genetically linked. It does, however, include a variety of phytochemicals, phenolic compounds, phytosterols, policosanols, and bioactive peptides [130]. Foxtail millet (*Setaria italica* Beauv) has antioxidant and anticancer properties and lowers cholesterol levels [131, 132]. Foxtail millet also has antihypertensive properties. Studies have also documented this cereal's hydrolyzed proteins' ability to suppress ACE [133]. Eating whole grains helps lower blood pressure. Forty-five middle-aged hypertensive patients who consumed 50 g of whole grains of pulverized foxtail millet extruded as bread or millet pancakes for 12 weeks showed a significant decrease in SBP of 133.61 and 129.48 mmHg as well as a

## *Immunomodulatory Plant Based Foods, It's Chemical, Biochemical and Pharmacological… DOI: http://dx.doi.org/10.5772/intechopen.112406*

decrease in the mass index and body fat [134]. Cereals have antihypertensive benefits because they improve endothelial function by blocking the effects of vasoconstrictors like Ang II itric oxide-based vasodilatation induced by substances like Ang II, which also affects the vasorelaxation tracts. In addition to the cereal already described, millet ingestion can support immune function modulation, which helps to guard against the COVID-19 illness [135].

### *2.2.2.4 Sorghum*

Tannins, phenolic acids, anthocyanins, and phytosterols are all present in sorghum (*Sorghum* spp.). These phytochemicals may have a major impact on human health by boosting cardiovascular health by lowering plasma levels of hepatic cholesterol and low-density lipoproteins [136]. Between 16 and 131 mg/g and 41 and 444 mg/g, respectively, of benzoic and cinnamic acids are present in sorghum [137]. The most researched sorghum flavonoids are anthocyanins. According to Awika et al. [138], black sorghum bran has anthocyanin levels at least twice as high as those of red sorghum (10.1 mg/g) and three to four times higher than those of whole grain. Though approximate concentrations of 44 to 72 mg/100 g have been reported [138, 139], there is a lack of quantitative information regarding the phytosterols contained in sorghum. The human immunodeficiency virus (HIV), herpes simplex 1 (VHS-1), hepatitis B and C (VHB/VHC), influenza A (H1N1), and, more recently, the virus that caused the COVID-19 disease (SARS-CoV-2) have all been shown to be susceptible to the antiviral effects of polyphenols [140]. In addition to having antiviral properties, phenolic chemicals also have antihypertensive properties. Irondi et al. [141] investigated the inhibitory activity of several enzymes, including ACE, in raw and toasted red sorghum grain flour (150 and 180°C). They discovered that the presence of phenolic acids (gallic, chlorogenic, caffeic, ellagic, and p-coumaric) and flavonoids (quercetin, luteolin, and apigenin) in high concentrations in raw grains led to their high inhibitory activities (19.64 g/mL), as increasing the temperature during toasting reduces the presence of phenolic compounds and, consequently, results in a decrease in inhibitory activity, having an IC50 of 20.99 g/mL in grains roasted at 150°C and 22.81 g/mL in grains roasted at 180°C. As a result, the corresponding decrease in the inhibitory activity of the enzymes and the phenolic composition of the grains with increasing toasting temperature shows that phenolic acids and flavonoids may be the primary inhibitors of the grain enzymes.

#### *2.2.3 Root and tubers*

Plants that produce starchy roots, tubers, rhizomes, corms, and stems are essential for human nutrition and health. In tropical places around the world, roots and tuber crops are essential agricultural staple energy sources, second only to cereals. They consist of potatoes, cassava, sweet potatoes, yams, and aroids, which are members of distinct botanical families but are grouped together. Several different carcinoma cell lines and animal models have shown that root and tuber phytochemicals have numerous pharmacology activities.

### *2.2.3.1 Yams (Dioscorea sp.)*

Yam are root crops that contain various bioactive substances with potential health benefits. They are rich in mucin, dioscin, dioscorin, allantoin, choline, polyphenols,

diosgenin, carotenoids, tocopherols, and vitamins [142, 143]. Yam extracts have demonstrated hypoglycemic, antibacterial, and antioxidant properties [144, 145]. They can increase the activity of digestive enzymes in the small intestine and promote the growth of stomach epithelial cells [146]. Additionally, yams have shown potential in bone marrow cell regeneration and splenocyte proliferation [147]. Dioscorin, a component of fresh yam (*Dioscorea batatas*), has exhibited DPPH radical scavenging activity and has been found to have beneficial effects in lowering blood pressure [148–150].

Yam cultivars also possess phenolic compounds that have antibacterial activity. Methanolic extracts from *Dioscorea* yams, such as *Dioscorea dumetorum* and *Dioscorea hirtiflora*, have demonstrated antioxidant and antibacterial activity [151]. In vitro studies using agar diffusion tests showed strong antibacterial activity against *Proteus mirabilis* by the nonedible *D. dumetorum*. Methanolic extracts from *D. hirtiflora* exhibited susceptibility against various species, including *Staphylococcus aureus*, *E. coli*, *Bacillus subtilis*, *P. mirabilis*, *Salmonella typhi*, *Candida albicans*, *Aspergillus niger*, and *Penicillium chrysogenum*.

Furthermore, dioscorin from yams has shown inhibitory and antihypertensive effects on the angiotensin-converting enzyme (ACE) in rats with spontaneous hypertension [143, 151]. Yam dioscorin has also displayed actions such as dehydroascorbate reductase (DHA), monodehydroascorbate reductase (MDA), trypsin inhibitor, and immunomodulatory effects [152, 153]. Chinese yam, in particular, contains diosgenin, an immunoactive steroidal saponin with prebiotic properties that promote the development of enteric lactic acid bacteria [154]. In animal studies, an ethanol extract of *Dioscorea alata* tubers exhibited antidiabetic action in rats with alloxan-induced diabetes [155]. Yam extract administered to diabetic rats resulted in lower creatinine levels, potentially improving renal function by reducing plasma glucose levels and subsequent glycosylation of renal basement membranes. Bioactive components of yam have also shown potential in reducing the risk of cancer and cardiovascular disorders in postmenopausal women [156]. Chronic administration of *Dioscorea* has been associated with changes in hormonal activities, bone remodeling, and improved bone strength [157].

### *2.2.3.2 Ipomoea batatas L. (sweet potato)*

Sweet potatoes (*I. batatas*) have their origins in Central America and are now widely cultivated in tropical and subtropical regions across the world. They are ranked as the seventh-largest food crop and can be grown throughout the year under ideal climatic conditions, making them a reliable "insurance crop" due to their resistance to complete crop loss from unfavorable weather conditions. The roots of sweet potatoes contain a soluble protein called sporamin, which constitutes 60–80% of the total proteins in the roots and serves as their primary protein store. Sporamin has been shown to possess antioxidant properties related to stress tolerance, including activities such as DHA and MDA reductase activities.

Alkaloids are another class of compounds found in sweet potatoes. Alkaloids are primarily used by plants as phytotoxins, antibacterials, insecticides, and fungicides to protect against feeding by insects, herbivorous animals, and mollusks. Commercial sweet potatoes mostly contain two glycoalkaloids, chaconine and solanine, which are glycosylated solonidine aglycone derivatives. Solasonine, a glycoalkaloid found in eggplants and wild potatoes (*Solanum chacoense*), belongs to the *Solanum* species.

### *Immunomodulatory Plant Based Foods, It's Chemical, Biochemical and Pharmacological… DOI: http://dx.doi.org/10.5772/intechopen.112406*

*Solanum* species have been found to possess various biological properties, including antitumor, antifungal, teratogenic, antiviral, and antiestrogenic activities. Some glycoalkaloids are even used as anticancer agents.

The peels of sweet potatoes have been reported by several authors to have potent wound healing effects, likely due to the free radical scavenging activity of the phytoconstituents and their ability to inhibit lipid oxidation. Studies conducted in rat models have shown that sweet potato fiber can have a positive impact on burn or decubital wounds, leading to changes in wound quantity and quality. In these studies, rats treated with sweet potato fiber coating showed smaller wound areas compared to the control group. Furthermore, a sweet potato petroleum ether extract was found to significantly reduce the amount of scarring necessary for complete epithelialization compared to the control. Human studies have explored the effects of consuming potatoes with different flesh colors on oxidative stress and inflammatory damage. In a randomized trial, participants were given white-, yellow-, or purple-fleshed potatoes once daily. The results indicated that the color of the potatoes affected oxidative stress and inflammatory damage, with purple-fleshed potatoes, high in anthocyanin and phenolic acids, showing positive effects. According to Hwang et al. [158], purple sweet potatoes have the potential to be effective in fighting obesity. Anthocyanin fractions from purple sweet potatoes were found to reduce the accumulation of hepatic lipids by activating the adenosine monophosphate-activated protein kinase (AMPK) signaling pathways. AMPK is a critical regulator of lipid production in metabolic tissues. In a study involving mice fed with purple sweet potatoes for 4 weeks, an intake of 200 mg/kg of body weight per day of anthocyanins led to decreased weight gain, reduced hepatic triacylglycerol buildup, and improved serum lipid parameters. The study also found that AMPK and acetyl coenzyme A carboxylase (ACC) were more frequently phosphorylated in the liver and HepG2 hepatocytes after anthocyanin treatment.

### *2.2.3.3 Cassava (Manihot esculenta)*

Cassava (*M. esculenta*) is the most extensively grown root crop in the tropics and can only be cultivated in tropical and subtropical regions due to its lengthy growth season, which typically ranges from 8 to 24 months. It belongs to the Euphorbiaceae family and is a perennial shrub. Among the 98 species that make up the genus *Manihot*, *M. esculenta* is the most widely cultivated species. The antioxidant properties of cassava roots have been the focus of several investigations. A recent study has highlighted that cassava tubers grown organically exhibited stronger antioxidant activities compared to roots treated with mineral-based fertilizers [159]. The researchers found that the total phenolic content (TPC) and flavonoid content (FC) of cassava cultivated with organic fertilizers were significantly higher than those of cassava treated with inorganic fertilizers. Antioxidants play a crucial role in protecting the body against oxidative stress and combating the damaging effects of free radicals. It is worth noting that cassava is primarily consumed as a staple food in many tropical regions, providing a significant source of carbohydrates. However, it is important to note that cassava contains cyanogenic glycosides, which are potentially toxic compounds. These compounds can release cyanide when consumed in large quantities or when cassava is prepared improperly. Therefore, proper processing methods such as soaking, fermenting, and cooking are essential to remove the cyanide content and make cassava safe for consumption.

## **2.3 Spices**

In addition to fruits and vegetables, spices and herbs are further sources of natural antioxidants [160]. Spices and herbs can be categorized using both taxonomical characteristics and flavor or taste. Depending on the taxonomic categorization, these spices and herbs are classified as either flowering plants or members of the Angiospermae class [161]. These herbs and spices are an abundant supply of phenolic compounds, and because of their useful characteristics, they are frequently used as food additives and in the pharmaceutical industry [162]. Spices' chemical constituents, which in turn depend on the polyphenolic content and bioactive chemicals, are responsible for their antioxidant activity [160].

## *2.3.1 Basil (Tulsi)*

In addition to preventing the growth of a variety of bacteria, yeasts, and molds, holy basil has been shown in a small research to improve immune system performance by raising certain immune cells in the blood. In addition to lowering blood sugar levels before and after meals and reducing anxiety and anxiety-related depression, holy basil has been linked to other health benefits. Reduces inflammation, reduces lipid peroxidation, and acts as an antioxidant [163].

## *2.3.2 Dill*

Dill and other greens are used to produce a variety of regional meals that are served with rotis or chapatis in India. Dill was a common ingredient in traditional treatments for a wide range of ailments, including jaundice, headaches, boils, a lack of appetite, stomach issues, nausea, liver issues, and many others. Additionally, dill seeds can be used to make herbal tea. Which contains antioxidative and antimicrobial activities [164].

## *2.3.3 Marjoram*

The tops of marjoram plants are trimmed as they start to flower and are then slowly dried in the shade. Marjoram is grown for its aromatic leaves, either green or dry, which are used in cooking. It is frequently combined with other herbs to make dishes like za'atar and herbes de Provence. Marjoram's flowering leaves and tops are steam-distilled to create an essential oil with a yellowish hue that eventually turns brown. It has a variety of chemical constituents, including pinene, borneol, and camphor. Antibacterial and antioxidant properties [165].

## *2.3.4 Thyme (Ajwain ke Phool)*

Common thyme (*Thymus vulgaris*) essential oil, known as oil of thyme, contains 20–54% thymol. Along with these extra substances, thyme essential oil also includes p-cymene, myrcene, borneol, and linalool. Listerine and other commercially available mouthwashes contain the antimicrobial thymol as an active component. Oil of thyme was employed to treat bandages before to the development of current antibiotics. Additionally, it has been demonstrated to work well against a number of fungi that frequently infect toenails. Some all-natural, alcohol-free hand sanitizers use thymol

as their main active ingredient [166]. The plant can be infused in water to create a tisane that can treat bronchitis and coughing. The antioxidant presence in thyme helps to prevent the loss of bone.

## *2.3.5 Rosmarinic acid*

Acid is the name of the rosemary's active component. It has been demonstrated that this chemical reduces nasal congestion and allergic reactions. In a study, rosmarinic acid doses of 50 and 200 mg were found to reduce allergy symptoms. Along with less congestion, nasal mucus' immune cell count fell. Anti-inflammatory, anti-carcinogen, decreased bone resorption, and antioxidant [167]. Herbs and spices are a great method to enhance the flavor of food without adding extra calories because they are naturally low in calories, fat, saturated fat, carbohydrates, and sodium. In reality, adding herbs and spices to food can help consumers' diets contain less harmful elements. Studies on the ethnopharmacology of spices' antioxidant and antiinflammatory effects on food and drinks [168] show that some of the most widely utilized natural antibacterial agents in food are in addition to these spices. Various spices contain natural substances that have antibacterial properties [169]. Because of this, steps must be done to control the issue by employing plant extracts that include photochemicals with antibacterial effects [170].

## *2.3.6 Garlic (Lehsun)*

*Allium sativum*, a member of the Alliance family, is thought to have its origins in Central Asia. To improve physical and mental health, it is used internationally as a flavoring ingredient, a traditional remedy, and a functional food. Antioxidant inhibits cerebral aging, decreases blood pressure, elevates HDL cholesterol, reduces inflammation, and strengthens immunity [170].

## *2.3.7 Ginger (Adrakh)*

Since ancient times, ginger, also known as *Zingiber officinale* Roscoe or Zingiberacae, has been used extensively in Chinese, Ayurvedic, and Tibb-Unani herbal medicines for a variety of unrelated ailments, such as arthritis, rheumatism, sprains, muscular aches and pains, sore throats, cramps, constipation, indigestion, vomiting, hypertension, dementia, fever, infectious diseases, and Antioxidant, alleviates knee osteoarthritis, antiemetic, anti-inflammatory, strengthens immunity, and antimicrobial (**Table 1**) [170].

## **3. Future perspective of medicinal plant and functional foods**

Given that there are around 500,000 plants in the world, most of which have not yet been investigated in medical practice, and given that both current and future research on medical activities may be successful in treating diseases, the future of medicinal herbs is bright. There is a long history of the use of medicinal plants; however, using the entire plant or raw materials for treatment or experimentation has many disadvantages, including changes in the plant's compounds in different climates, the concurrent development of synergistic compounds that lead to


#### **Table 1.**

*Therapeutic effects of spices in different diseases.*

antagonistic effects or other unexpected changes in bioactivity, and changes or loss of bioactivity due to variability and accumulation, storage, and preparation of raw materials.

However, novel approaches are therefore required to identify bioactive ingredients from medicinal plants and plant-based functional foods, evaluate their efficacy in human and animal models, and develop a sustainable and natural means of treating or preventing disease.

## **4. Conclusion**

Medicinal plant and plant-based functional foods have garnered significant interest due to their immune-enhancing properties and potential to address immune dysfunction. Extensive research has been conducted to understand the cellular and molecular mechanisms through which the bioactive ingredients in these foods exert their immune-enhancing effects. Compared to conventional drugs, plant-based functional foods offer several advantages, including lower risk of side effects, stability, and sustained efficacy.

By incorporating a variety of fruits and vegetables into our diet, such as mangoes, tomatoes, carrots, beetroot, bananas, grapes, apples, pomegranates, and oranges, we can benefit from their rich content of dietary fiber, vitamins, minerals, and

*Immunomodulatory Plant Based Foods, It's Chemical, Biochemical and Pharmacological… DOI: http://dx.doi.org/10.5772/intechopen.112406*

phytochemicals with potent antioxidant properties. These components have been associated with a reduced risk of chronic diseases, including heart disease, stroke, cancer, and age-related macular degeneration, as well as improved immune function.

Furthermore, exploring the potential of byproducts and waste materials from fruit and vegetable processing, such as peels and seeds, can lead to the discovery of additional bioactive compounds and contribute to reducing waste in the food industry. While medicinal plants and plant-based functional foods offer promising immune-enhancing properties, it is important to continue conducting research to fully understand their mechanisms of action and optimize their use in promoting overall health and well-being.

## **Author contributions**

Conceptualization, Bamidele S.O and Origbemisoye B.A Writing—original draft preparation, Bamidele S.O Writing—review and editing, Origbemisoye B.A and Akinbode B.A; authors have read and agreed to the published version of the manuscript.

## **Funding**

This research was not funded by any organization.

## **Conflict of interest**

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

## **Author details**

Bamidele Sekinat Olayem1 \*, Origbemisoye Babawande Olaitan1 and Akinbode Badiu Akinola<sup>2</sup>

1 Federal University of Technology, Akure, Ondo State, Nigeria

2 Gdansk University of Technology, Gdansk, Poland

\*Address all correspondence to: sekinatolayemi@gmail.com

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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## **Chapter 13**
