Since ages, humans have relied on nature for their basic amenities like comestibles, shelters, clothing, means of transportation, fertilizers, flavours, and fragrances, and not the least, medicines (Gurib-Fakim, 2006). Medicinal plants have formed the basis of sophisticated traditional medicinal practices, which have been used for thousands of years by people in China, India, Africa, and the rest of the world (Sneader, 2005). Early humans acquired the knowledge on plants’ therapeutic values through many years of vigilant observations, experience and trial and error experiments (Karunamoorthi et al., 2013a, 2012; Martin, 1995; Sofowora, 1982). Plant kingdom remains to be a repository of modern medicine due to their rich resource of bio-active molecules and secondary metabolites. Since time immemorial, each and every society has had their unique way of indigenous health practice system by using plants as a curative source to treat various ailments. However, the Chinese, Indian, and African traditional systems of medicine are globally renowned (Karunamoorthi et al., 2012).

The Ethiopian highlands, which are the most extensive of the African mountain region, are presumed to be covered by mountain forests. Historically, they have been coined as the water tower of east and northeast Africa - a notion, which refers to the fact that a number of rivers have their sources in the highlands. The Afromontane forests of Ethiopia, render ecological, socioeconomic and medicinal significance for the humankind. Ethiopia is rich in biodiversity with high endemism. The richness in flora and fauna is a reflection of the diverse ecological setting, climate and topography found in the country. The Ethiopian flora is estimated to contain 6500 to 7000 species of higher plants, of which about 12 percent are endemic. The country has the fifth largest flora in tropical Africa (Mekonnen and Hailemariam, 2000). Plants have been used as a source of medicine in Ethiopia from time immemorial to treat various ailments (Karunamoorthi and Tsehaye, 2012).

Genus Otostegia belongs to the family Lamiaceae, which consists of about 180 genera and over 3500 species. The Otostegia comprises about twenty species, among them fifteen are endemic to the northern part of tropical Africa and Southwestern and Central Asia, while the remaining five species have been reported in the flora of Ethiopia. Naturally, the species of Otostegia are medicinally decisive and, have been traditionally been used as an ophthalmia, mosquito repellency, antimicrobial, antihyperglyceamic, and antioxidant activity to prevent different kinds of sickness and disorders (Khan and Syed, 2013). Besides, its chemical constituents have also shown to possess antiulcer, antispasmodic, antidepressant, anxiolytic and sedative activities (Vural et al., 1996). In Ethiopia, O. integrifolia is commonly known by its vernacular name ‘Tinjute’ (Amharic - local language). It is an herbaceous plant that grows in the wild, but it is also cultivated in the gardens. The usage of plants for various day-to-day activities/ceremonies is deep-rooted in the Ethiopian tradition and culture and they use numerous plants as herbs to treat various sicknesses and disorders. Among them O. integrifolia is well-known for its pleasant odour, omnipotent medicinal values and insecticidal properties.

O. integrifolia is a synonym of Rydingia integrifolia (Benth.) Scheen and V.A. Albert. It is easily recognized and stands out due to the grayish color of the leaves. The yellow flowers are also showy when in full bloom (Getahun, 1976). It is one of the plants very often administered in the Ethiopian traditional system of medicine (Table 1).

[Table 1.] Scientific classification of Tinjute

Scientific classification of Tinjute

The essential oil and chloroform extract of air-dried leaves of O. integrifolia were investigated using analytical and preparative gas chromatography (GC), GC-mass spectrometry and Nuclear Magnetic Resonance techniques. A total of 40 constituents, including monoterpenes, sesquiterpenes, diterpenes and their derivatives were identified (Tesso and König, 2004). However, the five of the chemical compounds viz. axinyssene, otostegindiol, pretostegindiol, pentatriacontane and stigmasterol are observed to be the potential sources of pharmaceutics and medicine, to treat various illnesses (Fig. 1).

[Fig. 1.] Chemical compounds isolated from the O. integrifolia plant.

Over decades, the vector-borne diseases impose a serious public health concern to human beings in terms of considerable morbidity and mortality. The concomitant effects of global warming linked with climate change has further fueled the emergence and resurgence of several insect-borne diseases like malaria, plague, filariasis, trypanosomiasis, leishmaniasis and many arbo-viral diseases particularly dengue fever, yellow fever and chikungunya fever (Karunamoorthi, 2013). They account for nearly 17% of the global burden of infectious diseases (WHO, 2006). Besides, they also impose severe negative socioeconomic impact in the endemic regions (Karunamoorthi and Sabesan, 2009). Therefore, it is mandatory to minimize the global burden of these diseases by applying appropriate integrated vector control strategies and personal protection interventions.

An insect repellent is a substance applied to skin, clothing, or other surfaces to keep away insects from landing or climbing on that surface. The primary aim of the repellent usage is to reduce the man-vector contact and eventually to minimize the considerable annoying biting nuisance and disease transmission (Karunamoorthi and Sabesan, 2009). Repellents can be neither chemical nor natural (plant-based) and they are very supportive whenever and wherever other sorts of personal protection interventions are ineffective, unfeasible and impracticable (Karunamoorthi and Sabesan, 2010; Karunamoorthi et al., 2014). It is important to note that the existing synthetic repellents are usually inaccessible as well as unaffordable. Besides, they also pose a high level of residual toxicity and adverse side-effect (Karunamoorthi, 2011) for infants and elderly people and a few of them needed electricity also for their usage (Karunamoorthi et al., 2008a).

Since ancient time plants have been used to repel or kill the blood-sucking insects (Karunamoorthi et al., 2008b). Plant-based repellent products are easily available, locally known, and culturally acceptable (Karunamoorthi et al., 2010a). In Ethiopia, the rural population has often been using these plantbased materials as repellents by means of smoldering the dried plant parts (leaves, stem, root, bark and resin) on the traditional charcoal stove in the early evening to minimize the man-vector contact (Fig. 2). It is interesting to note that these low-cost repellant materials are abundantly obtainable in almost all the Ethiopian markets (Fig. 3). Ethnobotanical surveys in Ethiopia (Karunamoorthi et al., 2009a, b; Kidane et al., 2013; Teklay et al., 2013) and Eretria (Waka et al., 2004) found that the local residents have been using O. integrifolia as a potential traditional medicine to alleviate various illnesses and disorders (Kidane et al., 2013; Teklay et al., 2013) and insect repellent (Karunamoorthi et al., 2009a, b) to drive-away insects particularly mosquitoes by burning the dried plant parts as well as by hanging the plant around the main doors, windows and nearby sleeping cots in the early evening hours in Eretria (Waka et al., 2004).

[Fig. 2.] An Ethiopian women describing about the traditional usage of repellent plants by means of smoldering/burning on the traditional charcoal stove.

[Fig. 3.] Ethiopian vendors selling their repellant plants in the market of the Jimma town, Ethiopia .

In Ethiopia, an experiment was conducted by applying the smoke into the repellent “test” mosquito cage by direct burning of 25gm of dried leaves of O. integrifolia until plant materials are completely burnt. The result clearly revealed that the leaves of O. integrifolia have a potent repellent efficiency against Anopheles arabiensis, a principal malarial vector in Ethiopia (90.10%) and was the most effective (Karunamoorthi et al., 2008a). Since people have been using O. integrifolia for some medicinal purposes, no side effects have been reported. Therefore, it is suggested that this plant can be used as a safer alternative to modern synthetic chemical repellents against insect vector of diseases (Karunamoorthi et al., 2010).

The O. integrifolia has insecticidal properties and is often used as fumigant for pots and houses (Karunamoorthi et al., 2009a, b). Indeed the repellent activity of O. integrifolia was scientifically proved against An. arabiensis, however, further research/studies are warranted to examine, isolate, characterize and identify the untapped pool of bio-active molecules, which are accountable for the repellency effect. Furthermore, conducting more laboratory and field based studies are inevitable for human safety concerns (Karunamoorthi and Husen, 2012).These kinds of pioneer research could pave the way to formulate a new class of potent insect’ repellent from O. integrifolia in the near future (Karunamoorthi, 2012).

Over centuries, cultures around the world have learnt the usage of medicinal plants to fight against illness and to maintain good health. In the resource-limited settings, these plants are one of the longest-serving companions for the rural poor due to their easier accessibility and affordability (Karunamoorthi et al., 2013; Roberson, 2008). Despite the recent scientific advancement and globalization, the system of traditional medicine and complementary/alternative medicine is considered to be a primary health care modality in the resource-constrained health care settings (Roberson, 2008). The WHO estimates that, even now more than 80% of the world’s population relies on traditional healing modalities and herbals for primary health care and wellness (WHO, 2002). The heavy reliance on medicinal plants is partly owing to the high cost of modern drugs, limited or inaccessibility of modern healthcare facilities (Cunningham, 1993; WHO, 2003).

In the past, the importance of traditional medicinal plants and their phytotherapeutic values have often been disregarded and undervalued. However, in the recent years the revitalization and renewed interest on medicinal plants has been well-observed among the health conscious public and scientific community (Karunamoorthi et al., 2012), due to the long-term adverse consequences of modern chemotherapeutic agents. In Ethiopia, 70% and 90% of human and livestock population depend on the traditional system of medicine, respectively (Bekele, 2007).

Malaria continues to be a major global public health problem and about 3.3 billion people are at the risk in 104 endemic countries. It remains to be one of the important causes of maternal and childhood morbidity and mortality in sub-Saharan Africa and particularly Ethiopia (Karunamoorthi et al., 2010b).It is a disease of poverty and a cause of poverty which inflicts a serious negative impact on global public health and it has also hampered socioeconomic development among the poorest countries of the world (Karunamoorthi, 2012b).Globally, over thousand plants have been used as potential antimalarials in the resource-poor settings due to fragile/limited health-care systems, which quite often fail to meet the expectations of the needy poor people (Karunamoorthi et al., 2013b).

At the moment, there is a growing acceptance and keen interest towards traditional system medicines and it has led many researchers to concentrate on traditional antimalarial phytotherapy. Furthermore, the existing potent antimalarial artemisinin combination therapy is critically short supply unaffordable and inaccessible too. The recent reports suggest the emergence and spread of Plasmodium falciparum and Plasmodium vivax multidrug resistance malaria on Thailand-Myanmar and Thailand-Cambodia borders, the hotspot of multidrug resistance parasites (Bhumiratana et al., 2013; Karunamoorthi and Husen, 2012). Therefore, identifying the affordable and easily accessible potent antimalarials is a matter of grave concern. The analysis of traditional medicines that are employed for the treatment of malaria represents the potentiality for the discovery of lead molecules and henceforth for further development of potential antimalarial drugs (Muthaura et al., 2007). The new antimalarials are vital to combat and contain the emergence, resurgence and spread of multi-drug resistance strains in the near future.

In Ethiopian traditional medicine, the leaves of O. integrifolia are used for the treatment of several diseases including malaria. In an ongoing search for effective, safe and cheap antimalarial agents from plants, the 80% methanol leaf extract O. integrifolia was tested for its in vivo antimalarial activity against Plasmodium berghei. The results are encouraging and the extract exhibited potent antiplasmodial activity resulted in the isolation of a labdane diterpenoid identified as otostegindiol. Conclusively, the reputed antimalarial effect of O. integrifolia may be puted in whole or in part to the presence of the diterpenoid otostegindiol.

The genuine antiplasmodial activity along with its safety profile observed in the study could make the leaf extract of O. integrifolia a potential addition to the antimalarial armamentarium, and shall also provide a scientific support for the ethnomedicinal use of the plant (Endale et al., 2013). Besides, otostegindiol can be useful as a chemical and/or biological marker to guarantee the quality of the herbal product. Therefore, O. integrifolia may serve as potential candidates for the development of efficacious as well as safe phytomedicines (Endale et al., 2013).

Though many believe that the usages of medicinal plants are relatively safe, which have folklore reputations for antimalarial properties, many herbs may also be potentially toxic due to their intrinsic adverse side-effects. Therefore herbal-derived remedies need a powerful and deep assessment of their pharmacological qualities in order to establish their mode of action, safety, quality and efficacy. World-wide, over thousand plant species have been used as a source of traditional antimalarial phytotherapy for many centuries and in the future, plant-derived compounds will still be an essential aspect of the therapeutic array of antimalarials. However, their clinical efficacy, quality and safety need to be scientifically evaluated and proved (Karunamoorthi et al., 2013b).

Research has indicated that one of the chemical constituents of O. integrifolia called stigmasterol may be useful in prevention of certain cancers, including ovarian, prostate, breast, and colon cancers. Studies with laboratory animals fed stigmasterol found that both cholesterol and sitosterol absorption decreased 23% and 30%, respectively. It was demonstrated that it inhibits several pro-inflammatory and matrix degradation mediators typically involved in osteoarthritis-induced cartilage degradation (Gabay et al., 2010). It also possesses potent antioxidant, hypoglycemic and thyroid inhibiting properties (Panda et al., 2009). Stigmasterol is the precursor of anabolic steroid boldenone and oldenone undecylenate is commonly used in veterinary medicine to induce growth in cattle, but it is also one of the most commonly abused anabolic steroids in sports (Draisci et al., 2007; Gallina et al., 2007; Ros et al., 2007). In Saudi Arabia, the irritated eyes of cows, goats, and sheep can be rinsed with leaf infusion of the O. integrifolia (Abulafatih, 1987). The roots of O. integrifolia are used for treating lung diseases too.

Though utilization of medicinal plants is not a new phenomenon, now there is more consciousness among the people about the adverse effects of synthetic products as well user-friendly nature of plant-based products than ever before. In Ethiopia, O. integrifolia is one of the reputable plants for its phytotherapeutic potentialities and insecticidal properties. However, there are only a limited number of studies have been reported to authenticate the omnipotent properties of O. integrifolia, particularly, its traditional usage as antimalarial, disinfectant and insecticidal agents. Therefore, further studies are warranted by using the existing modern scientific methods and innovative techniques to prove the potency, safety and feasibility in the future.