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Botanical features and ethnopharmacological potential of Leonotis nepetifolia (L.) R. Br: a review
J Plant Biotechnol 2022;49:3-14
Published online March 31, 2022
© 2022 The Korean Society for Plant Biotechnology.

Roggers Gang·Youngmin Kang

University of Science & Technology (UST), Korean Convergence Medicine, Daejeon, Republic of Korea
Korea Institute of Oriental Medicine (KIOM), Yuseongdae-ro, Yuseong-gu, Daejeon, Republic of Korea
National Semi-Arid Resources Research Institute (NaSARRI), P.O Box 56, Soroti, Uganda
Correspondence to: e-mail: ymkang@kiom.re.kr

Equally contributed to this manuscript and should be considered co-first authors.
Received November 6, 2021; Revised January 7, 2022; Accepted January 7, 2022.
cc This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Leonotis nepetifolia (L.) R. Br, commonly called dagga, klip dagga, or lion’s ear, has been used to effectively treat various diseases and other health problems for a long time because of its antimicrobial, anti-inflammatory, antioxidant, and analgesic activities. Several studies have attributed these biological activities to L. nepetifolia’s constituent secondary metabolites, such as alkaloids, phenolics, flavonoids, tannins, steroids, glycosides, coumarins, anthocyanins, and saponins. This review aims to examine the evidence-based ethnopharmacological uses of L. nepetifolia in the treatment of bronchial asthma, diarrhea, skin diseases, malaria, burns, cancer, diabetes mellitus, and rheumatism. However, although L. nepetifolia has great potential to treat these diseases, further isolation and identification of its therapeutic phytochemical constituents are required. In addition, the performance of its extracts and phytochemicals should be thoroughly tested in preclinical and clinical trials in order to ascertain their safety and efficacy, which will prove valuable in developing new medicines.
Keywords : ethnopharmacological, Leonotis nepetifolia, klip dagga, lion’s ear, phytochemicals, secondary metabolites, biological activity
Introduction

Medicinal plants are major components of indigenous medical systems worldwide. For several years, medicinal plants have been used to treat diseases (da Silva Almeida et al. 2018). As reported by the World Health Organization (WHO), 80% of people in the world use herbal medicines in the management of their primary healthcare needs (Bhardwaj et al. 2018; Majeed 2017). In addition to their use in traditional medicine, medicinal plants are sources of new drugs; indeed, more than 25% of prescribed drugs in developed countries are wild plant species derived (Chen et al. 2016). Furthermore, approximately 70%-80% of the people in the developing world rely on conventional plant-derived remedies (Rankoana 2016). Given the growing demand for herbal drugs, natural health products, and plant secondary metabolites, the use of medicinal plants is rapidly increasing globally (Chen et al. 2016).

Leonotis nepetifolia (L.) R. Br (family Lamiaceae, genus Leonotis) (Damasceno et al. 2019), also called ‘dagga’, ‘klip dagga’, or ‘lion’s ear’, is a plant species native to South Africa with significant medicinal value (Dhawan et al. 2013). The plant has become widespread in many tropical regions around the world (Pushpan and Karra 2016). In many traditional health practices, L. nepetifolia is used to treat bronchial asthma, diarrhea, fever, influenza, malaria, cough, epilepsy, womb prolapse, skin ailments, and rheumatism (da Silva Almeida et al. 2018; Oliveira et al. 2015). The therapeutic power of L. nepetifolia has been attributed to its phytochemical contents, including alkaloids, tannins, saponins, flavonoids, steroids, and terpenoids (Li et al. 2012; Ngoci et al. 2013; Powder-George 2018; Sobolewska et al. 2012). Several studies have confirmed that these phytochemicals protect humans against disease-causing organisms (Njeru et al. 2013). The phytochemical compounds present in the plant are associated with a variety of bioactivities, such as antimicrobial, immunomodulatory, anti-cancer, antioxidant, analgesic, and anti-inflammatory (Ngocu et al. 2012; Oliveira et al. 2015).

However, the literature on evidence-based ethnopharmacological uses of L. nepetifolia is currently limited and scattered. This review aimed to examine evidence-based ethnopharmacological uses of L. nepetifolia in the treatment of bronchial asthma, diarrhea, diabetes, cancer, malaria, skin diseases, burns, and rheumatism, to provide consolidated medicinal information about the plant and to facilitate further research and its medicinal applications.

Materials and Methods

The literature was searched as in Komakech et al. (2017) after modifications to find information about L. nepetifolia from peer-reviewed articles published in scientific journals (Figure 1) with a focus on botany, distribution, and ethnopharmacological and traditional medicinal uses of L. nepetifolia. Google Scholar, PubMed, Scopus, AMED, and Science Direct databases were searched in order to acquire relevant and reliable data. The key search terms used included (“Leonotis nepetifolia (L.) R. Br” OR “Dagga - Klip dagga” OR “Lion’s ear”) AND (“Botany” OR “Distribution” OR “Phytochemicals” OR “Phytochemical compounds” OR “Phytochemical contents” OR “Ethnopharmacological uses” OR “Ethno-medicinal uses” OR “Disease treatment” OR “Safety and Toxicity” OR “Traditional medicine” OR “Medicine”). Search results were verified for accuracy and reliability, then summarized, analyzed, and compared; finally, appropriate conclusions were drawn.

Fig. 1. Summary of the review methodology followed in this study
Botany and Distribution of L. nepetifolia

L. nepetifolia is an erect annual herb that grows 2.5 m high, occasionally reaching up to 3 m (Figure 2a). The stem is unbranched at the base and loosely branched towards the apex with strongly angled stems having appressed retrose hairs that are longer at the nodes (Figure 2b) (Dhawan et al. 2013). The leaves are smooth with a toothed margin; they are large, ovate, lobed, acute, and winged in the upper part (Figure 2d and 2e). The inflorescence comprises axillary dense, globose multi-flowered verticillasters (Tiwari 2019). Flowers are orange and borne in spiny clusters. Floral leaves are lanceolate and deflexed; bracts are linear, highly spinous-pointed, and deflexed (Figure 2c). Calyxes are tubular, incurved, and hairy with 8-9 sharp pointed teeth. The plant typically has a bilabiate, orange-scarlet and hairy corolla with the upper lip densely woody, and the lower lip made up of three lobes. Stamens are four and didynamous; the ovary has four lobes and the fruit contains four ovoid nutlets (Tiwari 2019).

Fig. 2. Botanical features of L. nepetifolia: (a) plant growing in the wild, (b) stem characteristics and leaf arrangement, (c) inflorescence, (d) features of the upper leaf surface, (e) features of the lower leaf surface, and (f) seeds

Genus Leonotis consists of 30 species found mostly in the tropics. Among them, L. nepetifolia is the only species distributed out of Africa (Iwarsson and Harvey 2003). Indeed, the species has a pantropical global distribution, and can be found in Africa, Southeast Asia, Australia, the Pacific islands, Southern USA, Central and South America, the Caribbean islands, and Mexico (Pushpan and Karra 2016).

Ethnopharmacological Uses of L. nepetifolia

In traditional medicine, L. nepetifolia is used to treat many diseases including bronchial asthma, diarrhea, fever, influenza, malaria, cough, womb prolapse, epilepsy, burns, skin ailments, and rheumatism (Table 1). Constituent phytochemicals such as tannins, alkaloids, flavonoids, saponins, steroids, phenolics, glycosides, anthocyanins, and coumarins have been implicated to account for the usefulness of the plant to treat the abovementioned diseases (Ngoci et al. 2013) (Table 2). Importantly, the antimicrobial, immunomodulatory, anti-cancer, antioxidant, analgesic, and anti-inflammatory activities of these phytochemicals have been confirmed both in vitro and in vivo (Ngocu et al. 2012; Oliveira et al. 2015), as discussed below.

Diseases treated using L. nepetifolia, plant parts used, and modes of administration

Diseases treated Plant part (s) used Mode of administration References
Malaria Whole plant or leaves Decoction; infusion; leaf tea Adia et al. (2014), Anywar et al. (2014), Ferreira et al. (2015), Kumar and Dash (2012), Wagh (2016)
Diarrhea Flowers and leaves Decoction; powder taken in porridge or tea Kingo and Maregesi (2020), Omwenga et al. (2015), Tugume et al. (2019)
Asthma Stem, leaves, and flowers Decoction; powder of the flower taken in porridge or tea Clement et al. (2005), Kingo and Maregesi (2020), Maregesi et al. (2007), Olanda et al. (2020)
Skin infections Leaves, seeds, inflorescence, root, and whole plant Paste applied topically Anbarashan et al. (2011), Kalaichelvi et al. (2017), Li et al. (2012), Maurya and Seth (2014), Nadu (2019), Prashantkumar and Vidyasagar (2008), Rao et al. (2006), Sharma et al. (2014), Singh and Shahi (2017), Van Andel and Van’t Klooster (2007)
Wounds, burns, and scalds Flowers and leaves Powder or ash applied topically Kalaichelvi et al. (2017), Krishna et al. (2014), Maregesi et al. (2007), Mudaiya et al. (2016), Pingale et al. (2013), Rao et al. (2006)
Rheumatism Leaves, whole plant, flowers, and seeds Infusion; decoction; paste applied locally Kalaichelvi et al. (2017), Li et al. (2012), Mallick and Acharya (2013), Nayak et al. (2004), Pandey and Tripathi (2010), Pereira et al. (2012), Pingale et al. (2013), Pushpan et al. (2013), Reddy et al. (2019), Singh and Shahi (2017), Ssegawa and Kasenene (2007), Tiwari et al. (2018)
Cancer Whole plant or leaves Decoction Kalaichelvi et al. (2017), Kingo and Maregesi (2020), Nadu (2019)
Diabetes Whole plant or leaves Decoction Kumar and Jnanesha (2017), Maobe (2014), Pingale et al. (2013)
Fever Whole plant or leaves Brewed as a tea Kalaichelvi et al. (2017), Li et al. (2012), Veerabadran et al. (2013)
Cough Leaves and inflorescence Brewed as a tea; boiled to a viscous paste and orally administered Li et al. (2012), Pandey and Tripathi (2010), Veerabadran et al. (2013)
Uterine prolapse Leaves Brewed as a tea Veerabadran et al. (2013)
Menstrual pains and period dysregulation Whole plant a Jain and Srivastava (2005), Lans (2007)
Jaundice Stem, leaves, and flowers Infusion Jain and Srivastava (2005), Pingale et al. (2013)
Parasitic worm infections Leaves Decoction Jain and Srivastava (2005)
Convulsions Leaves Boiled in water and drunk; decoction Maregesi et al. (2007)
Postnatal breast pain Inflorescence Ash mixed with mustard oil and applied topically Tiwari et al. (2018)
Pneumonia Whole plant a EL-Kamali (2009), Nadu (2019)
Syphilis Whole plant a Nadu (2019)
Labor pains Leaves Chewed; boiled in water and drunk Catherine et al. (2020)
Paralysis Whole plant Ash applied topically Mallick and Acharya (2013), Nayak et al. (2004), Singh and Shahi (2017)
Hepatitis Whole plant Decoction EL-Kamali (2009), Mukazayire et al. (2011), Pingale et al. (2013)
Hernia Leaves a Pingale et al. (2013)

aNot specified.

Source: adapted from Kang et al. (2013).



Some phytochemical compounds identified in L. nepetifolia and their biological activities

Phytochemical compounds Plant part Biological activities References
Leonotinin Leaves Anti-inflammatory, hepatoprotective, and antihypercholestrolemic activity Parra-Delgado et al. (2004)
Stigmasterol Flower Anti-inflammatory, hepatoprotective, and antihypercholestrolemic activity Parra-Delgado et al. (2004)
Nepetaefuran and leonotinin Aerial part Anti-inflammatory and antitumor activity Ueda et al. (2015)
Methoxy-nepetaefolin hydroxy-dialactone nepetaefolinol, dehydrated nepetaefolinol, and nepetefolin Aerial part Antioxidant activity Govindasamy et al. (2002), Tidke et al. (2021)
Phenylethanoid glycosides, acteoside, martynoside, lavanduflioside, 10-o-(trans-3,4-dimethoxycinnamoyl) geniposidic acid, geniposidic acid, mussaenoside, and ixoside Stem Antioxidant activity Takeda et al. (1999)
Loganin and loganic acid Stem α-Glucosidase inhibition Tidke et al. (2021)
Cirsiliol Leaves and root Antileishmanial and antimicrobial activity de Oliveira et al. (2019), Tidke et al. (2021)
Apigenin Leaves, stem, and root Antiviral, antileishmanial, and antimicrobial activity de Oliveira et al. (2019)
Luteolin Leaves and stem Antileishmanial and antimicrobial activity de Oliveira et al. (2019)


Ethnopharmacological Uses of L. nepetifolia for Treatment of Malaria

Malaria is among the top causes of morbidity and mortality in the world. Approximately 219 million cases of malaria and 435,000 associated deaths were registered in 2017 (Ghosh and Rahi 2019). Several ethnomedicinal studies have reported that the whole L. nepetifolia plant is widely used to treat malaria in many communities worldwide (Adia et al. 2014; Anywar et al. 2014; Ferreira et al. 2015; Wagh 2016). In this case, either the decoction, leaf tea, or leaf infusion, is given for treatment (Anywar et al. 2014; Ferreira et al. 2015; Wagh 2016). The effective use of L. nepetifolia in the traditional treatment of malaria is linked to the presence of secondary metabolites including tannins, alkaloids, flavonoids, glycosides, and saponins, which are the active constituents responsible for the antimalarial activity (Musila et al. 2013). In vitro and in vivo studies on Plasmodium falciparum 3D7 strain and on mice infected with Plasmodium berghei revealed that plant extracts with these secondary metabolites showed strong antiplasmodial activity (Abdillah et al. 2015). Alkaloids exhibit antimalarial effects by blocking protein synthesis in malarial parasites (Abdulelah and Zainal-Abidin 2007). In turn, steroids and saponins have been confirmed to be damaging to many pathogenic protozoans, including P. falciparum, P. ovale, and P. vivax (Delmas et al. 2000). Additionally, an in vitro antiplasmodial study showed that tannins have antiplasmodial activity (Adia et al. 2014). Further, another study showed that methanol and ethyl acetate extracts of L. nepetifolia leaf had moderate antiplasmodial activity with 27% inhibition of P. falciparum and low cytotoxic effects on the MRC5 cell line (Lacroix et al. 2011). These findings vindicate the use of L. nepetifolia in traditional medicine for the treatment of malaria.

Ethnopharmacological Uses of L. nepetifolia for Treatment of Diarrhea

Diarrhea is very common in countries of the developing world, and in Southeast Asia and Africa alone, it causes 8.5% and 7.7%, respectively, of all deaths (Dairo et al. 2017). In fact, diarrheal diseases rank second on the list of major causes of death among children under the age of five, worldwide (Fenta et al. 2020). To manage the disease, L. nepetifolia has traditionally been used in the treatment of diarrhea across Africa, where L. nepetifolia powdered flowers or leaf ashes are added to porridge or tea, and in some cases decoction of L. nepetifolia is consumed (Kingo and Maregesi 2020; Omwenga et al. 2015; Tugume et al. 2019). In an in vitro test, L. nepetifolia leaf, flower, and stem methanolic extracts showed antibacterial activity against Shigella dysenteriae, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Micrococcus luteus, Shigella flexneri, Vibrio cholerae, and Staphylococcus aureus, which are some of the main bacterial pathogens that cause diarrhea (Narayan 2012). The study thus demonstrated the presence of broad-spectrum antibacterial compounds in the leaves, flowers, and stems of the species. Inhibition of bacterial growth by plant extracts is attributed to alkaloids, saponins, tannins, flavonoids, sterols, and terpenoids present in different plant parts (Boominathan et al. 2005; Otshudi et al. 2000). Tannic acids and tannins reportedly denature proteins, which in turn form protein tannate, a substance that makes intestinal mucosa resistant, thus reducing secretions and subsequently reducing diarrhea (Narayan 2012). Ethanolic leaf extracts of L. nepetifolia showed diarrhea inhibitory activity at doses of 225, 450, and 900 mg/kg in Wistar albino rats (Gakunga et al. 2013). In this study, the extract produced a significant (p < 0.05) reduction in the number of wet fecal pellets and a greatly reduced diarrheal tendency (Gakunga et al. 2013). Further, Gakunga et al. (2013) found that the ethanolic leaf extract of L. nepetifolia had an inhibitory effect on gastrointestinal transit by reducing the mean distance traveled by a charcoal meal, which has a propulsive effect; however, L. nepetifolia extracts inhibited this effect in the intestinal tract by significantly reducing the mean distance traveled upon administration of 225 mg/kg (p = 0.01). At a dose of 900 mg/kg, gastrointestinal transit was significantly (p < 0.05) inhibited relative to that in the positive control, atropine sulfate (Gakunga et al. 2013). It should be noted that fluid accumulation and altered motility of the gastrointestinal tract cause diarrhea; therefore, numerous antidiarrheal medicines work by inhibiting these processes. Indeed, extracts of L. nepetifolia caused a similar inhibition of diarrhea to that caused by the standard drug loperamide (3 mg/kg) in terms of the number of wet fecal droppings (Gakunga et al. 2013). Therefore, these findings support the traditional use of L. nepetifolia for treatment of diarrhea.

Ethnopharmacological Uses of L. nepetifolia for Treatment of Bronchial Asthma

Asthma is currently an umbrella diagnosis for a number of distinct diseases and varying phenotypes manifesting symptoms of shortness of breath, cough, wheezing, and chest tightness associated with variable airflow obstruction (Kuruvilla et al. 2019; Reddel et al. 2015). Technically, asthma is an inflammatory disorder of epithelial surfaces that typically involves allergen-driven T-helper 2 (Th2) lymphocyte polarization with coordinated production of interleukin (IL)-3, IL-13, IL-4, IL-9, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF), which are encoded in a gene cluster on chromosome 5q31–34 (Holgate and Polosa 2006). Asthma is a major chronic disease worldwide, affecting more than 334 million people (Enilari and Sinha 2019) and accounting for approximately one in every 250 deaths (Tany and Saha 2017). The use of traditional medicines in the management of asthma is increasing markedly, and L. nepetifolia is among the plants said to have a high potential for treatment of the disease (Akah et al. 2003). Thus, stem, leaves, and flowers of L. nepetifolia are used in the treatment of asthma; a decoction is swallowed, or powdered flowers are added to porridge or tea and consumed (Kingo and Maregesi 2020; Maregesi et al. 2007; Olanda et al. 2020). Utilization of L. nepetifolia to treat and manage asthma is supported by the fact that flavonoids present in various parts of L. nepetifolia have been shown to control some specific allergic reactions in asthma and other conditions (Maregesi et al. 2007). The mechanisms of action of L. nepetifolia against asthma include enhancing intracellular glutathione (GSH) content, reducing reactive oxygen species (ROS) levels, and preventing Ca2+ influx in cases of high ROS levels, and, consequently, offering protection against oxidative damage (Athwal et al. 2015; Garcia et al. 2005; Lambrechts et al. 2018). Further, Lall et al. (2019) reported that L. nepetifolia was among the plants that exhibited a level of antioxidant activity similar to that of the positive control, L-ascorbic acid. Generally, the antioxidant potential of plants, including L. nepetifolia, is attributed to the antioxidative phenolics found in the plant tissues (Lall et al. 2019). Sobolewska et al. (2012) in their study reported that methanolic and acetone extracts of L. nepetifolia contained moderate levels of polyphenols. Thus, the oxidative and anti-inflammatory properties of secondary metabolites in L. nepetifolia provide support for the use of L. nepetifolia for management and treatment of bronchial asthma.

Ethnopharmacological Uses of L. nepetifolia for Treatment of Skin Diseases

Skin diseases including ringworm, leprosy, itching, wounds, dermatitis, allergy, swelling, eczema, psoriasis, and scabies, are caused by various microorganisms or harsh environments (Suresh et al. 2012); further, they account for approximately 34% of all occupational diseases (Abbasi et al. 2010). Infectious dermatological diseases are highly prevalent in tropical countries where the majority of the population lives in developing areas characterized by poor sanitation and unhygienic food habits (Sharma et al. 2014). Morbidity due to skin diseases causes emotional and psychological stress to patients and their families, although mortality is very low (Basra and Shahrukh 2009). Numerous medicinal plants have been traditionally used to treat skin diseases, L. nepetifolia among them (Prashantkumar and Vidyasagar 2008). Ethnobotanical surveys conducted around the world revealed that L. nepetifolia has been used for a long time to treat skin diseases, such as eczema, head sores, urticaria, ringworm, itching, burns, scalds, and wounds (Anbarashan et al. 2011; Nadu 2019; Singh and Shahi 2017). Treatment preparations include leaf paste, seed paste (in some places mixed with “Koronji” oil), inflorescence paste (sometimes mixed with groundnut oil), root paste, whole plant paste, powdered dry leaves, and flower ashes. During treatment, the preparation is applied topically (Kalaichelvi et al. 2017; Nadu 2019; Singh and Shahi 2017).

The extensive use of L. nepetifolia by different societies in the treatment of skin diseases is likely due to its effectiveness (Maroyi 2013). Previous studies have reported antifungal and antibacterial activities of plant extracts (Al-Reza et al. 2010; Bajpai 2012; Ngoci et al. 2013). Thus, for example, in an in vivo study by Ochola et al. (2015), the extract of L. nepetifolia demonstrated antifungal effects by inhibiting the growth of P. exigua mycelia. Additionally, as noted earlier, an in vitro test of flower, leaf, and stem methanolic extracts of L. nepetifolia showed antibacterial properties against Staphylococcus aureus, a pathogen that causes eczema (Narayan 2012). In general, plants with a wide range of secondary metabolites, such as tannins, flavonoids, alkaloids, terpenoids, and polyphenols, possess superior antimicrobial properties (Maiyo et al. 2010) and, indeed L. nepetifolia is rich in these phytochemicals. In an in vivo experiment, L. nepetifolia ethanol-treated wounds healed significantly faster than the negative control, with an increased rate of contraction and a reduced epithelialization period (Nithya and Anand 2021). Plants with high anti-inflammatory and wound healing potential, and their products, contain terpenes and flavonoids (Nithya and Anand 2021). The strong wound-healing effects of medicinal plants are attributed to their constituent triterpenoids (Nayak et al. 2006). Flavonoids and terpenoids enhance wound healing mainly through their antimicrobial activities (Nithya and Anand 2021). Therefore, the wound-healing activities observed in the preclinical trial may be due to the flavonoids and terpenoids present in L. nepetifolia. Generally, these results support the widespread use of L. nepetifolia for treatment of skin diseases.

Ethnopharmacological Uses of L. nepetifolia for Treatment of Rheumatism

Musculoskeletal disorders, such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, systemic lupus erythematosus, gout, and intervertebral disc disease, among others, are generally categorized as “rheumatism.” The diagnosis and treatment of these conditions make up approximately 10% of clinical practice (Pushpan et al. 2013). The use of L. nepetifolia for treatment of rheumatism has been extensively recorded among different communities. In this case, leaves, the whole plant, flowers or seeds are used (Mallick and Acharya 2013; Reddy et al. 2019; Tiwari et al. 2018) with multiple modes of administration including, infusion, decoction, or local application of paste for treating arthritis (Nayak et al. 2004; Pushpan et al. 2013; Tiwari et al. 2018). In a preclinical study, traditional and modified dosages of whole plant decoctions of L. nepetifolia showed significant effects (p < 0.05) on secondary edema and inhibitory effects on Freund’s adjuvant-induced arthritis (Pushpan et al. 2017). The dry aqueous extract-treated group showed significantly decreased secondary paw edema on the 20th and 25th days, and the decoction showed similar results. The test drugs produced values similar to those of the standard drug on the 25th day of the secondary edema experiment. These findings demonstrate the beneficial effects of L. nepetifolia on chronic inflammation, periarthritis, and osteogenic activity. Leonotinin present in L. nepetifolia was identified as the active phytochemical with distinct anti-inflammatory activity (Parra-Delgado et al. 2004). In addition, Makambila-Koubemba et al. (2011) reported that stigmasterol and leonotinin isolated from L. nepetifolia showed significant anti-inflammatory properties (p < 0.05). Furthermore, the anti-inflammatory effect of L. nepetifolia was also attributed to flavonoids. In another study, Parra-Delgado et al. (2004) evaluated the anti-inflammatory properties of some extracts and isolates from L. nepetifolia in a TPA-induced edema model. This study evaluated the ability of L. nepetifolia extracts to block an inflammatory reaction to edemogen 12-O-tetradecanoylphorbol-13-acetate (TPA). In this case, all tested extracts exhibited anti-inflammatory effects in the TPA-induced edema test in mice, and the highest activity was observed in the ethyl acetate (EtOAc) extracts of leaves, flowers, and stems (65.75%, 69.06%, and 72.93% anti-inflammatory activity, respectively). Anti-inflammatory activity was attributed to stigmasterol, whose anti-inflammatory activity is well documented (Akihisa and Yasukawa 2001). Thus, these studies suggest that the popular claim for the use of the whole plant of L. nepetifolia for treatment of rheumatism is legitimate.

Ethnopharmacological Uses of L. nepetifolia treatment of Cancer

Cancer is one of the worst health problems globally (Subastri et al. 2018). Approximately 20 million people are diagnosed with cancer annually, and over 6 million mortalities are registered (Gurunagarajan and Pemaiah 2011). Natural products, including herbs, have been used to treat and prevent cancer (Oliveira et al. 2019). Studies have shown that decoctions of the whole plant or leaves of L. nepetifolia are administered as anticancer and antitumor agents in several communities (Kalaichelvi et al. 2017; Kingo and Maregesi 2020; Nadu 2019). Oliveira et al. (2019) reported that flavonoid 30,40,5-trihydroxy-6,7-dimethoxyflavone (cirsiliol), a constituent of L. nepetifolia, is one of the anticancer molecules; specifically, the molecule has selective cytotoxic activity on human tumor-cell lines SF-295, HL-60, and OVCAR8 (Bai et al. 2010; Li et al. 2012). In an in vitro study, Gurunagarajan and Pemaiah (2011) evaluated the anticancer potential of L. nepetifolia and Hyptis suaveolens Poit. against the Ehrlich ascites carcinoma (EAC) cell line. Ethanolic extracts from both plants proved cytotoxic to EAC cells. In fact, 500 μg/mL ethanolic extracts of L. nepetifolia (EELN) had a significantly higher percentage cytotoxicity (80.86%) compared to that (75.21%) of ethanolic extracts of Hyptis suaveolens Poit (EEHS) at the same concentration. Cell death caused by the plant extracts was attributed to the loss of mitochondria, one of the major markers of apoptosis (Potten 1992). Further, through DNA fragmentation analysis, both EELN and EEHS exhibited effective fragmentation of the DNA of EAC, implying that EELN can trigger apoptosis in cancer cells (Gurunagarajan and Pemaiah 2011). In another study, Vasuki et al. (2016) investigated the in vitro antioxidant properties of L. nepetifolia whole-plant ethanolic extracts using the hydroxyl radical DPPH, and nitric oxide radical scavenging methods. Due to the fact that free radicals are associated with such different acute and chronic diseases as cancer, atherosclerosis, and diabetes mellitus (Athar 2002), antioxidants are known to provide resistance to oxidative stress through free radical scavenging activity. Vasuki et al. (2016) found that the ethanolic extract of L. nepetifolia exhibited an in vitro antioxidant effect at a concentration of 20 μg/mL. The highest antioxidant activity was against nitric oxide radicals (77.07% ± 1.77% inhibition; IC50 = 2.03 μg/mL), followed by activity against DPPH radicals (64.47% ± 1.42% inhibition; IC50 = 3.07 μg/mL), and activity against hydroxyl radicals (62.96% ± 1.78% inhibition; IC50 = 7.55 μg/mL). Similarly, Prakash et al. (2014) studied methanolic leaf extracts for free radical scavenging activity against DPPH, and the antioxidant ability of L. nepetifolia was portrayed. Sobolewska et al. (2012) also obtained results consistent with Gurunagarajan and Pemaiah (2011) regarding anti-cancer activity in their in vitro analysis of the cytotoxicity of L. nepetifolia acetone and methanolic extracts towards human prostate-cancer cell line DU145. The median effective doses (ED50) for AE after 24 h and 48 h of incubation were 60 and 40 μg/mL, respectively. Notably, 100% cell mortality was recorded after 48 h at a concentration of 200 μg/ml of the extract. On the other hand, the ED50 for ME after 24 and 48 h of incubation were 100 and 60 μg/mL, respectively. Labdane-type diterpenes found in the aerial parts of L. nepetifolia reportedly have cytotoxic activity and are known as cell-cycle inhibitors and apoptosis inducers (Mahaira et al. 2011) so L. nepetifolia AE and ME cytotoxicity towards human prostate-cancer cell line DU145 may be linked to this class of compounds. Further, Veerabadran et al. (2013) conducted an in vitro investigation of the antioxidant and anticancer potential of L. nepetifolia extracts and reported that the leaf methanolic extract had significant free radical scavenging activity with 60.57% inhibition, a percentage similar to that of the standard reference. Furthermore, the extract damaged cancer cell lines MCF-7 and Hep2 in a dose-dependent manner. A DNA fragmentation assay showed significant fragmentation at concentrations of 2.5 and 1.25 mg/mL, thus confirming that the mechanism whereby the extract inhibits the growth of Hep2 cells involves DNA fragmentation. Consistently, remarkable DNA fragmentation was detected in MCF 7 cells at a concentration of 125 μg/mL. These activities were associated with flavonoids because the compound has been confirmed to have a wide range of biological and chemical activities (Miliauskas et al. 2004). These findings fully justify the use of L. nepetifolia for cancer treatment.

Ethnopharmacological Uses of L. nepetifolia for treatment of Diabetes mellitus

Diabetes mellitus (DM) is a metabolic disorder characterized by high blood-glucose concentrations and glucose excretion in the urine (Maobe 2014). The forms of DM are type 1 and type 2, where type 1 DM is a result of the autoimmune destruction of the pancreatic beta cells that produce insulin, consequently, people with type 1 DM require insulin for survival (Imperatore et al. 2021). Meanwhile, type 2 DM is mainly caused by a combination of insulin resistance and relative insulin deficiency (American Diabetes Association 2017). By 2013, 10% of the world population was recorded as suffering from diabetes (Maobe 2014). Some studies have reported that L. nepetifolia is used to treat diabetes in traditional systems of medicine where the whole plant or the leaf decoction is administered to the patients (Kumar and Jnanesha 2017; Maobe 2014; Pingale et al. 2013). Ethanolic extracts of the whole plant L. showed significant (p ≤ 0.05) antidiabetic activity in an alloxan rat model (Gungurthy et al. 2013). This antidiabetic activity exhibited might be due to one or more of the following activities: enhanced tissue glucose-uptake, improved pancreatic beta-cell function, or inhibited intestinal glucose-absorption (Gungurthy et al. 2013). Marrubiin, a diterpenoid lactone, is a constituent of L. nepetifolia known to have anti-diabetic properties (Mnonopi et al. 2012). Strong evidence suggests that marrubiin increases insulin secretion and low-density lipoprotein cholesterol (Popoola et al. 2013). In another study, marrubiin showed a significant increase in insulin and glucose transporter-2 gene expression in vivo (Stulzer et al. 2006). These results partly explain the effectiveness of L. nepetifolia in the treatment of diabetes mellitus.

Conclusions

L. nepetifolia is an important medicinal plant used to treat several diseases and other health problems around the world. Numerous studies have established the therapeutic potency of some of the phytochemical compounds found in L. nepetifolia for treatment of bronchial asthma, diarrhea, skin diseases, malaria, burns, cancer, diabetes mellitus, and rheumatism. The findings summarized herein provide solid evidence of the effectiveness of L. nepetifolia for treating these diseases. However, we cannot say that the whole phytochemical composition of this plant in each of its parts is fully known at present. In light of this, we recommend the isolation, and accurate and reliable identification of the therapeutic phytochemical constituents present in the different parts of the L. nepetifolia plant, coupled with additional preclinical and clinical studies, to confirm their safety and efficacy for use in the development of new drugs.

Acknowledgements

This research was funded by Development of Sustainable Application for Standard Herbal Resources (KSN2013320), Korea Institute of Oriental Medicine through the Ministry of Science and ICT, Republic of Korea.

Conflicts of Interest

The authors declare no conflict of interest in the publication of this review paper.

Figures
Fig. 1. Summary of the review methodology followed in this study
Fig. 2. Botanical features of L. nepetifolia: (a) plant growing in the wild, (b) stem characteristics and leaf arrangement, (c) inflorescence, (d) features of the upper leaf surface, (e) features of the lower leaf surface, and (f) seeds
Tables
Table. 1.

Diseases treated using L. nepetifolia, plant parts used, and modes of administration

Diseases treated Plant part (s) used Mode of administration References
Malaria Whole plant or leaves Decoction; infusion; leaf tea Adia et al. (2014), Anywar et al. (2014), Ferreira et al. (2015), Kumar and Dash (2012), Wagh (2016)
Diarrhea Flowers and leaves Decoction; powder taken in porridge or tea Kingo and Maregesi (2020), Omwenga et al. (2015), Tugume et al. (2019)
Asthma Stem, leaves, and flowers Decoction; powder of the flower taken in porridge or tea Clement et al. (2005), Kingo and Maregesi (2020), Maregesi et al. (2007), Olanda et al. (2020)
Skin infections Leaves, seeds, inflorescence, root, and whole plant Paste applied topically Anbarashan et al. (2011), Kalaichelvi et al. (2017), Li et al. (2012), Maurya and Seth (2014), Nadu (2019), Prashantkumar and Vidyasagar (2008), Rao et al. (2006), Sharma et al. (2014), Singh and Shahi (2017), Van Andel and Van’t Klooster (2007)
Wounds, burns, and scalds Flowers and leaves Powder or ash applied topically Kalaichelvi et al. (2017), Krishna et al. (2014), Maregesi et al. (2007), Mudaiya et al. (2016), Pingale et al. (2013), Rao et al. (2006)
Rheumatism Leaves, whole plant, flowers, and seeds Infusion; decoction; paste applied locally Kalaichelvi et al. (2017), Li et al. (2012), Mallick and Acharya (2013), Nayak et al. (2004), Pandey and Tripathi (2010), Pereira et al. (2012), Pingale et al. (2013), Pushpan et al. (2013), Reddy et al. (2019), Singh and Shahi (2017), Ssegawa and Kasenene (2007), Tiwari et al. (2018)
Cancer Whole plant or leaves Decoction Kalaichelvi et al. (2017), Kingo and Maregesi (2020), Nadu (2019)
Diabetes Whole plant or leaves Decoction Kumar and Jnanesha (2017), Maobe (2014), Pingale et al. (2013)
Fever Whole plant or leaves Brewed as a tea Kalaichelvi et al. (2017), Li et al. (2012), Veerabadran et al. (2013)
Cough Leaves and inflorescence Brewed as a tea; boiled to a viscous paste and orally administered Li et al. (2012), Pandey and Tripathi (2010), Veerabadran et al. (2013)
Uterine prolapse Leaves Brewed as a tea Veerabadran et al. (2013)
Menstrual pains and period dysregulation Whole plant a Jain and Srivastava (2005), Lans (2007)
Jaundice Stem, leaves, and flowers Infusion Jain and Srivastava (2005), Pingale et al. (2013)
Parasitic worm infections Leaves Decoction Jain and Srivastava (2005)
Convulsions Leaves Boiled in water and drunk; decoction Maregesi et al. (2007)
Postnatal breast pain Inflorescence Ash mixed with mustard oil and applied topically Tiwari et al. (2018)
Pneumonia Whole plant a EL-Kamali (2009), Nadu (2019)
Syphilis Whole plant a Nadu (2019)
Labor pains Leaves Chewed; boiled in water and drunk Catherine et al. (2020)
Paralysis Whole plant Ash applied topically Mallick and Acharya (2013), Nayak et al. (2004), Singh and Shahi (2017)
Hepatitis Whole plant Decoction EL-Kamali (2009), Mukazayire et al. (2011), Pingale et al. (2013)
Hernia Leaves a Pingale et al. (2013)

aNot specified.

Source: adapted from Kang et al. (2013).


Table. 2.

Some phytochemical compounds identified in L. nepetifolia and their biological activities

Phytochemical compounds Plant part Biological activities References
Leonotinin Leaves Anti-inflammatory, hepatoprotective, and antihypercholestrolemic activity Parra-Delgado et al. (2004)
Stigmasterol Flower Anti-inflammatory, hepatoprotective, and antihypercholestrolemic activity Parra-Delgado et al. (2004)
Nepetaefuran and leonotinin Aerial part Anti-inflammatory and antitumor activity Ueda et al. (2015)
Methoxy-nepetaefolin hydroxy-dialactone nepetaefolinol, dehydrated nepetaefolinol, and nepetefolin Aerial part Antioxidant activity Govindasamy et al. (2002), Tidke et al. (2021)
Phenylethanoid glycosides, acteoside, martynoside, lavanduflioside, 10-o-(trans-3,4-dimethoxycinnamoyl) geniposidic acid, geniposidic acid, mussaenoside, and ixoside Stem Antioxidant activity Takeda et al. (1999)
Loganin and loganic acid Stem α-Glucosidase inhibition Tidke et al. (2021)
Cirsiliol Leaves and root Antileishmanial and antimicrobial activity de Oliveira et al. (2019), Tidke et al. (2021)
Apigenin Leaves, stem, and root Antiviral, antileishmanial, and antimicrobial activity de Oliveira et al. (2019)
Luteolin Leaves and stem Antileishmanial and antimicrobial activity de Oliveira et al. (2019)

References
  1. Abbasi AM, Khan M, Ahmad M, Zafar M, Jahan S, Sultana S (2010) Ethnopharmacological application of medicinal plants to cure skin diseases and in folk cosmetics among the tribal communities of North-West Frontier Province. Pakistan. J Ethnopharmacol 128(2): 322-335
    Pubmed CrossRef
  2. Abdillah S, Tambunan RM, Farida Y, Sandhiutami NMD, Dewi RM (2015) Phytochemical screening and antimalarial activity of some plants traditionally used in Indonesia. Asian Pacific Journal of Tropical Disease 5(6): 454-457
    CrossRef
  3. Abdulelah H, Zainal-Abidin B (2007) In vivo anti-malarial tests of Nigella sativa (black seed) different extracts. Am J Pharmacol Toxicol 2(2): 46-50
    CrossRef
  4. Adia MM, Anywar G, Byamukama R, Kamatenesi-Mugisha M, Sekagya Y, Kakudidi EK, Kiremire BT (2014) Medicinal plants used in malaria treatment by Prometra herbalists in Uganda. J Ethnopharmacol 155(1): 580-588
    Pubmed CrossRef
  5. Akah P, Ezike A, Nwafor S, Okoli C, Enwerem N (2003) Evaluation of the anti-asthmatic property of Asystasia gangetica leaf extracts. J Ethnopharmacol 89(1): 25-36
    Pubmed CrossRef
  6. Akihisa T, Yasukawa K (2001) Antitumor-promoting and anti-inflammatory activities of triterpenoids and sterols from plants and fungi. Studies in natural products chemistry 25: 43-87
    CrossRef
  7. Al-Reza SM, Rahman A, Lee J, Kang SC (2010) Potential roles of essential oil and organic extracts of Zizyphus jujuba in inhibiting food-borne pathogens. Food Chem 119(3): 981-986
    CrossRef
  8. American Diabetes Association (2017) Classification and diagnosis of diabetes. Diabetes care 40: 11-24
    Pubmed CrossRef
  9. Anbarashan M, Parthasarthy N, Padmavathy A (2011) Ethno-floristic survey in sacred groves, Pudukottai district, Tamil Nadu-India. Journal of Medicinal Plants Research 5(3): 439-443
  10. Anywar G, Oryem-Origa H, Mugisha MK (2014) Wild plants used as nutraceuticals from Nebbi district, Uganda. European Journal of Medicinal Plants: 641-660
    CrossRef
  11. Athar M (2002) Oxidative stress and experimental carcinogenesis. Indian Journal of Experimental Biology 40: 656-667
    Pubmed
  12. Athwal RK, Walkiewicz MP, Baek S, Fu S, Bui M, Camps J, Ried T, Sung M-H, Dalal Y (2015) CENP-A nucleosomes localize to transcription factor hotspots and subtelomeric sites in human cancer cells. Epigenetics & chromatin 8(1): 1-23
    Pubmed KoreaMed CrossRef
  13. Bai N, He K, Zhou Z, Lai C-S, Zhang L, Quan Z, Shao X, Pan M-H, Ho C-T (2010) Flavonoids from Rabdosia rubescens exert anti-inflammatory and growth inhibitory effect against human leukemia HL-60 cells. Food Chem 122(3): 831-835
    CrossRef
  14. Bajpai V (2012) In Vitro and In Vivo Inhibition of Plant Pathogenic Fungi by Essential Oil and Extracts of Magnolia liliflora Desr. Journal of Agricultural Science and Technology 14(4): 845-856
  15. Basra MK, Shahrukh M (2009) Burden of skin diseases. Expert Review of Pharmacoeconomics & Outcomes Research 9(3): 271-283
    Pubmed CrossRef
  16. Bhardwaj S, Verma R, Gupta J (2018) Challenges and future prospects of herbal medicine. International Research in Medical and Health Sciences 1(1): 12-15
    CrossRef
  17. Boominathan R, Devi B, Dewanjee S, Mandal S (2005) Studies on antidiarrhoeal activity of Ionodium suffruticosam ging.(violaceae) extract in rats. Recent Progress in Medicinal Plants (Phytotherapeutics) 10: 375-380
  18. Catherine K, Mugisha KM, Bright W, Engeu OP, Kahwa I (2020). Documentation and Phytochemical Screening of Most Commonly used Nutri-Medicinal Plants by Pregnant Women in Kyeizooba, Bushenyi District, Western Uganda
  19. Chen S-L, Yu H, Luo H-M, Wu Q, Li C-F, Steinmetz A (2016) Conservation and sustainable use of medicinal plants: problems, progress, and prospects. Chinese medicine 11(1): 1-10
    Pubmed KoreaMed CrossRef
  20. Clement YN, Williams AF, Aranda D, Chase R, Watson N, Mohammed R, Stubbs O, Williamson D (2005) Medicinal herb use among asthmatic patients attending a specialty care facility in Trinidad. BMC Complementary and Alternative Medicine 5(1): 1-8
    Pubmed KoreaMed CrossRef
  21. da Silva Almeida JRG, de Menezes Barbosa J, Cavalcante NB, Delange DM (2018) A review of the chemical composition and biological activity of Leonotis nepetifolia (Linn.) R. Br.(lion’s ear). Revista Cubana de Plantas Medicinales 23(4)
  22. Dairo MD, Ibrahim TF, Salawu AT (2017) Prevalence and determinants of diarrhoea among infants in selected primary health centres in Kaduna north local government area, Nigeria. Pan African Medical Journal 28(1): 151-151
    Pubmed KoreaMed CrossRef
  23. Damasceno LM, Silva AL, Santos RFd, Feitosa TA, Viana LG, Oliveira-Júnior RGd, Silva M, Rolim L, Araújo C, Araújo E (2019) Cytotoxic activity of chemical constituents and essential oil from the leaves of Leonotis nepetifolia (Lamiaceae). Rev Virtual Quim 11: 517-528
    CrossRef
  24. Delmas F, Di Giorgio C, Elias R, Gasquet M, Azas N, Mshvildadze V, Dekanosidze G, Kemertelidze E, Timon-David P (2000) Antileishmanial activity of three saponins isolated from ivy, α-hederin, β-hederin and hederacolchiside A1, as compared to their action on mammalian cells cultured in vitro. Planta Medica 66(04): 343-347
  25. de Oliveira DP, de Almeida L, Marques MJ, de Carvalho RR, Dias ALT, da Silva GA, de Pádua RM, Braga FC, da Silva MA (2019) Exploring the bioactivity potential of Leonotis nepetifolia: phytochemical composition, antimicrobial and antileishmanial activities of extracts from different anatomical parts. Natural product research: 1-6
    Pubmed CrossRef
  26. Dhawan NG, Khan AS, ivastava P Sr (2013) A general appraisal of Leonotis nepetifolia (L) R. Br: an essential medicinal plant. Bulletin of Environment, Pharmacology and Life Sciences 2(8): 118-121
  27. EL-Kamali HH (2009) Medicinal plants in east and central Africa: challenges and constraints. Ethnobotanical Leaflets 2009(2): 12
  28. Enilari O, Sinha S (2019) The global impact of asthma in adult populations. Annals of global health 85(1)
    Pubmed KoreaMed CrossRef
  29. Fenta A, Alemu K, Angaw DA (2020) Prevalence and associated factors of acute diarrhea among under-five children in Kamashi district, western Ethiopia: community-based study. BMC pediatrics 20: 1-7
    Pubmed KoreaMed CrossRef
  30. Ferreira AB, Ming LC, Haverroth M, Daly DC, Caballero J, Ballesté AM (2015) Plants Used to Treat Malaria in the Regions of Rio Branco-Acre State and Southern Amazonas State-Brazil. International Journal of Phytocosmetics and Natural Ingredients 2(1): 9-9
  31. Gakunga NJ, Kateregga G, Sembajwe LF, Kateregga J (2013) Antidiarrheal activity and phytochemical profile of the ethanolic leaf extract of Leonotis nepetifolia (Lion’s ear) in Wistar albino rats. Journal of Complementary Medicine Research 2(2): 121-126
  32. Garcia V, Arts I, Sterne J, Thompson R, Shaheen SO (2005) Dietary intake of flavonoids and asthma in adults. Eur Respir J 26(3): 449-452
    Pubmed CrossRef
  33. Ghosh SK, Rahi M (2019) Malaria elimination in India—the way forward. Journal of vector borne diseases 56(1): 32
  34. Govindasamy L, Rajakannan V, Velmurugan D, Banumathi S, Vasanth S (2002) Structural studies on three plant diterpenoids from Leonotis nepetaefolia. Crystal Research and Technology. Journal of Experimental and Industrial Crystallography 37(8): 896-909
  35. Gungurthy J, Sabbathi S, Chaitanya KB, Ravella A, Ramesh C (2013) Antidiabetic activity of Leonotis nepetifolia Lin. in alloxan induced diabetic rats. Inter J Preclin Pharma Res 4(1): 5-9
  36. Gurunagarajan S, Pemaiah B (2011) Comparative studies on cytotoxic effect of Hyptis suaveolens Poit. and Leonotis nepeatefolia R. Br. against EAC cell lines. Journal of Pharmacy Research 4(4): 1222-1224
  37. Holgate ST, Polosa R (2006) The mechanisms, diagnosis, and management of severe asthma in adults. The Lancet 368(9537): 780-793
    Pubmed CrossRef
  38. Imperatore G, Mayer-Davis EJ, Orchard TJ, Zhong VW (2021). Prevalence and incidence of type 1 diabetes among children and adults in the United States and comparison with non-US countries
    CrossRef
  39. Iwarsson M, Harvey Y (2003) Monograph of the genus Leonotis (Pers.) R. Br.(Lamiaceae). In: Kew bulletin, pp 597-645
  40. Jain S, ivastava S Sr (2005). Traditional uses of some Indian plants among islanders of the Indian Ocean
  41. Kalaichelvi K, Dhivya S, Shalini PV (2017) Indigenous Knowledge on Herbicious Medicinal Plants among the Local People of Mavanathan and Ittarai Villages, Thalamalai Hills, Sathyamangalam Reserve Forest Ranage, Tamil Nadu, India. Int J Plant Anim Environ Sci 7(3): 10-18
  42. Kingo RM, Maregesi SM (2020). Ethnopharmacological Study on Some Medicinal Plants Used in Ujiji, Kigoma, Tanzania
  43. Komakech R, Kang Y, Lee J-H, Omujal F (2017). A review of the potential of phytochemicals from Prunus africana (Hook f.) Kalkman stem bark for chemoprevention and chemotherapy of prostate cancer. Evidence-Based Complementary and Alternative Medicine 2017
  44. Krishna NR, Varma Y, Saidulu C (2014) Ethnobotanical Studies of Adilabad District, Andhra Pradesh, India. Journal of Pharmacognosy and Phytochemistry 3(1)
  45. Kumar A, Jnanesha A (2017) Cultivation, Utilization and Role of Medicinal Plants in Tradition Medicine in Deccan Eco-climate. International Journal on Agricultural Sciences 8(1): 98-103
  46. Kumar S, Dash D (2012) Flora of Nandan Kanan Sanctuary: Medicinal plants with their role in Health care. International Journal of Pharmacy & Life Sciences 3(4)
  47. Kuruvilla ME, Lee FE-H, Lee GB (2019) Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol 56(2): 219-233
    Pubmed KoreaMed CrossRef
  48. Lacroix D, Prado S, Kamoga D, Kasenene J, Namukobe J, Krief S, Dumontet V, Mouray E, Bodo B, Brunois F (2011) Antiplasmodial and cytotoxic activities of medicinal plants traditionally used in the village of Kiohima, Uganda. J Ethnopharmacol 133(2): 850-855
    Pubmed CrossRef
  49. Lall N, van Staden AB, Rademan S, Lambrechts I, De Canha MN, Mahore J, Winterboer S, Twilley D (2019) Antityrosinase and anti-acne potential of plants traditionally used in the Jongilanga community in Mpumalanga. S Afr J Bot 126: 241-249
    CrossRef
  50. Lambrechts D, Wauters E, Boeckx B, Aibar S, Nittner D, Burton O, Bassez A, Decaluwé H, Pircher A, Van den Eynde K (2018) Phenotype molding of stromal cells in the lung tumor microenvironment. Nat Med 24(8): 1277-1289
    Pubmed CrossRef
  51. Lans C (2007) Ethnomedicines used in Trinidad and Tobago for reproductive problems. Journal of ethnobiology and ethnomedicine 3(1): 1-12
    Pubmed KoreaMed CrossRef
  52. Li J, Fronczek FR, Ferreira D, Burandt CL Jr, Setola V, Roth BL, Zjawiony JK (2012) Bis-spirolabdane diterpenoids from Leonotis nepetaefolia. J Nat Prod 75(4): 728-734
    Pubmed KoreaMed CrossRef
  53. Mahaira LG, Tsimplouli C, Sakellaridis N, Alevizopoulos K, Demetzos C, Han Z, Pantazis P, Dimas K (2011) The labdane diterpene sclareol (labd-14-ene-8, 13-diol) induces apoptosis in human tumor cell lines and suppression of tumor growth in vivo via a p53-independent mechanism of action. Eur J Pharmacol 666(1-3): 173-182
    Pubmed CrossRef
  54. Maiyo Z, Ngure R, Matasyoh J, Chepkorir R (2010) Phytochemical constituents and antimicrobial activity of leaf extracts of three Amaranthus plant species. African Journal of Biotechnology 9(21): 3178-3182
  55. Majeed M (2017) Evidence-based medicinal plant products for the health care of world population. Annals of Phytomedicine 6(1): 1-4
    CrossRef
  56. Makambila-Koubemba M-C, Mbatchi B, Ardid D, Gelot A, Henrion C, Janisson R, Abena AA, Banzouzi J-T (2011) Pharmacological studies of ten medicinal plants used for analgesic purposes in Congo Brazzaville. International journal of pharmacology 7(5): 608-615
    CrossRef
  57. Mallick S, Acharya B (2013). Phytodiversity survey of roadside herbs and their ethno-medicinal values in and around Rourkela Steel Township, Sundargarh, Odisha Life Sciences Leaflets 35:46 to 55-46 to 55
    CrossRef
  58. Maobe MAGM (2014). Standardization of Selected Medicinal Herbs from Kisii Region Used in Treatment of Diabetes, Malaria and Pneumonia
    CrossRef
  59. Maregesi SM, Ngassapa OD, Pieters L, Vlietinck AJ (2007) Ethnopharmacological survey of the Bunda district, Tanzania: Plants used to treat infectious diseases. J Ethnopharmacol 113(3): 457-470
    Pubmed CrossRef
  60. Maroyi A (2013) Traditional use of medicinal plants in south-central Zimbabwe: review and perspectives. Journal of ethnobiology and ethnomedicine 9(1): 1-18
    Pubmed KoreaMed CrossRef
  61. Maurya SK, Seth A (2014) Potential medicinal plants and traditional ayurvedic approach towards urticaria, An allergic skin disorder. Int J Pharm Pharm Sci 6(5): 172-177
  62. Miliauskas G, Venskutonis P, Van Beek T (2004) Screening of radical scavenging activity of some medicinal and aromatic plant extracts. Food Chem 85(2): 231-237
    CrossRef
  63. Mnonopi N, Levendal R-A, Mzilikazi N, Frost C (2012) Marrubiin, a constituent of Leonotis leonurus, alleviates diabetic symptoms. Phytomedicine 19(6): 488-493
    Pubmed CrossRef
  64. Mudaiya RK, Lale SK, Shankar R, Dhiman K (2016) Medicinal Wealth of Dindori Forest Division of Madhya Pradesh, India need conservation and systemic collection. World Jour of Pharmaceutical Res 5(2): 347-372
  65. Mukazayire M-J, Minani V, Ruffo CK, Bizuru E, Stévigny C, Duez P (2011) Traditional phytotherapy remedies used in Southern Rwanda for the treatment of liver diseases. J Ethnopharmacol 138(2): 415-431
    Pubmed CrossRef
  66. Musila M, Dossaji S, Nguta J, Lukhoba C, Munyao J (2013) In vivo antimalarial activity, toxicity and phytochemical screening of selected antimalarial plants. J Ethnopharmacol 146(2): 557-561
    Pubmed CrossRef
  67. Nadu T (2019). Ethnomedicinal Plants of Gopalswamy Hills, Western Ghats, Coimbatore District, Tamilnadu
    CrossRef
  68. Narayan S (2012) Antibacterial potential of crude methanolic extract of Leonotis nepetifolia (L) R. Br. International Research Journal of Pharmacy 3(2): 277-278
  69. Nayak S, Behera SK, Misra MK (2004). Ethno-medico-botanical survey of Kalahandi district of Orissa
  70. Nayak S, Nalabothu P, Sandiford S, Bhogadi V, Adogwa A (2006) Evaluation of wound healing activity of Allamanda cathartica. L. and Laurus nobilis. L. extracts on rats. BMC complementary and alternative medicine 6(1): 1-6
    Pubmed KoreaMed CrossRef
  71. Ngoci N, Evalyne M, Ng’ang’a E (2013) Screening for anti-bacterian activity and phytochemicals of Leonotis nepetifolia leaves methanol extract. Journal of Biotechnological Sciences: 15-21
  72. Ngocu SN, Mwaniki CG, Mwendia CM, Matasyoh JC (2012) Screening of Indigofera lupatana Baker F. root extracts for antibacterial activities. African Journal of Pharmacology and Therapeutics 1(3)
  73. Nithya V, Anand K (2021). Wound Healing activity of Leonotis nepetaefolia r. br., in wistar albino rats
  74. Njeru SN, Matasyoh J, Mwaniki CG, Mwendia CM, Kobia K (2013) A Review of some phytochemicals commonly found in medicinal plants. Int J Med Plant 105: 135-140
  75. Ochola S, Ogendo J, Wagara I, Ogweno J, Nyaanga J, Ogayo K (2015) Antifungal activity of methanol extracts of Leonotis nepetifolia L. and Ocimum gratissimum L. against Ascochyta blight (Phoma exigua) on French bean. Asian Journal of Plant Pathology 9(1): 27-32
    CrossRef
  76. Olanda RF, Barroso EB, Gavilanes ML, Silva EO (2020) Medicinal plants used in the Santo Antônio dos Pretos quilombola community (Codó Municipality, Maranhão, Brazil). Revista Ibero-Americana de Ciências Ambientais 11(3): 392-401
  77. Oliveira AP, Silva AL, Viana LG, Silva MG, Lavor ÉM, Oliveira-Júnior RG, Alencar-Filho EB, Lima RS, Mendes RL, Rolim LA (2019) β-Cyclodextrin complex improves the bioavailability and antitumor potential of cirsiliol, a flavone isolated from Leonotis nepetifolia (Lamiaceae). Heliyon 5(10)
    Pubmed KoreaMed CrossRef
  78. Oliveira DM, Melo FG, Balogun SO, Flach A, de Souza ECA, de Souza GP, Rocha IdNA, da Costa LAMA, Soares IM, da Silva LI (2015) Antibacterial mode of action of the hydroethanolic extract of Leonotis nepetifolia (L.) R. Br. involves bacterial membrane perturbations. J Ethnopharmacol 172: 356-363
    Pubmed CrossRef
  79. Omwenga E, Hensel A, Shitandi A, Goycoolea F (2015) Ethnobotanical survey of traditionally used medicinal plants for infections of skin, gastrointestinal tract, urinary tract and the oral cavity in Borabu sub-county, Nyamira county, Kenya. J Ethnopharmacol 176: 508-514
    Pubmed CrossRef
  80. Otshudi AL, Vercruysse A, Foriers A (2000) Contribution to the ethnobotanical, phytochemical and pharmacological studies of traditionally used medicinal plants in the treatment of dysentery and diarrhoea in Lomela area, Democratic Republic of Congo (DRC). J Ethnopharmacol 71(3): 411-423
    Pubmed CrossRef
  81. Pandey AK, Tripathi N (2010) Diversity and distribution of aromatic plants in forests of Gorakhpur division, UP, India. In: In: Biol Forum Int J Vol. 2 Citeseer, pp 25-33
  82. Parra-Delgado H, García Ruiz G, Nieto Camacho A, Martínez-Vázquez M (2004) Anti-inflammatory activity of some extracts and isolates from Leonotis nepetaefolia on TPA-induced edema model. Revista de la Sociedad Química de México 48(4): 293-295
  83. Pereira FL, Fernandes JM, Leite JPV (2012) Ethnopharmacological survey: a selection strategy to identify medicinal plants for a local phytotherapy program. Brazilian Journal of Pharmaceutical Sciences 48: 299-313
    CrossRef
  84. Pingale R, Pokharkar D, Phadtare S (2013) A Review on Ethnopharmacolgy, Phytochemistry and Bioactivity of Leonitis Nepatofolia. International J PharmTech Res 5(3): 1161-1164
  85. Popoola OK, Elbagory AM, Ameer F, Hussein AA (2013) Marrubiin. Molecules 18(8): 9049-9060
    Pubmed KoreaMed CrossRef
  86. Potten CS (1992) The significance of spontaneous and induced apoptosis in the gastrointestinal tract of mice. Cancer and metastasis reviews 11(2): 179-195
    Pubmed CrossRef
  87. Powder-George Y (2018) Secondary Metabolites from the leaves and stems of Leonotis nepetifolia (Lamiaceae). Trop J Nat Prod Res 2(6): 293-296
    CrossRef
  88. Prakash NU, Bhuvaneswari S, ipriya N Sr, Prameela L, Bhagya R, Radhika B, Balamurugan A, Arokiyaraj S (2014) Antioxidant activity of common plants of Northern Tamil Nadu, India. International Journal of Pharmacy and Pharmaceutical Sciences 6(4): 128-132
  89. Prashantkumar P, Vidyasagar G (2008). Traditional knowledge on medicinal plants used for the treatment of skin diseases in Bidar district, Karnataka
  90. Pushpan R, Karra N (2016). Granthiparni Vis-À-Vis Leonotis nepetifolia (L.) R. Br-A Review on Source Identification
  91. Pushpan R, Karra N, Nariya MB, Ashok B (2017) Evaluation of anti-arthritic potential of Leonotis nepetifolia (L.) R. Br. against Freund’s adjuvant induced arthritis. Journal of Ayurveda and Integrated Medical Sciences 2(05): 59-66
  92. Pushpan R, Nishteswar K, Kumari H (2013) Anti-arthritic natural medicine: Classical Ayurvedic and ethnomedical source. ASL Muscuskel Dis 1: 32-40
    CrossRef
  93. Rankoana SA (2016) Curative care through administration of plant-derived medicines in Sekhukhune District Municipality of Limpopo province, South Africa. African Journal of Traditional, Complementary and Alternative Medicines 13(2): 47-51
    CrossRef
  94. Rao R, Sagar K, Syamasundar K (2006) Wild aromatic plant species of western ghats: Diversity, conservation and utilization. In: In: International Seminar on Multidisciplinary Approaches in Angiosperm Systematics, pp 358-371
  95. Reddel HK, Bateman ED, Becker A, Boulet L-P, Cruz AA, Drazen JM, Haahtela T, Hurd SS, Inoue H, De Jongste JC (2015) A summary of the new GINA strategy: a roadmap to asthma control. Eur Respir J 46(3): 622-639
    Pubmed KoreaMed CrossRef
  96. Reddy AM, Babu MVS, Rao RR (2019) Ethnobotanical study of traditional herbal plants used by local people of Seshachalam Biosphere Reserve in Eastern Ghats, India. Herba Polonica 65(1)
    CrossRef
  97. Sharma J, Gairola S, Sharma YP, Gaur R (2014) Ethnomedicinal plants used to treat skin diseases by Tharu community of district Udham Singh Nagar, Uttarakhand, India. J Ethnopharmacol 158: 140-206
    Pubmed CrossRef
  98. Singh RS, Shahi SK (2017) Diversity of medicinal plants of Ratanpur region of Bilaspur district (Chhattisgarh). J Med Plants 5: 276-281
  99. Sobolewska D, Paśko P, Galanty A, Makowska-Wąs J, Padło K, Wasilak W (2012) Preliminary phytochemical and biological screening of methanolic and acetone extracts from Leonotis nepetifolia (L.) R. Br. Journal of Medicinal Plants Research 6(30): 4582-4585
    CrossRef
  100. Ssegawa P, Kasenene JM (2007) Medicinal plant diversity and uses in the Sango bay area, Southern Uganda. J Ethnopharmacol 113(3): 521-540
    Pubmed CrossRef
  101. Stulzer HK, Tagliari MP, Zampirolo JA, Cechinel-Filho V, Schlemper V (2006) Antioedematogenic effect of marrubiin obtained from Marrubium vulgare. J Ethnopharmacol 108(3): 379-384
    Pubmed CrossRef
  102. Subastri A, Arun V, Sharma P, Suyavaran A, Nithyananthan S, Alshammari GM, Aristatile B, Dharuman V, Thirunavukkarasu C (2018) Synthesis and characterisation of arsenic nanoparticles and its interaction with DNA and cytotoxic potential on breast cancer cells. Chem-Biol Interact 295: 73-83
    Pubmed CrossRef
  103. Suresh M, Ayyanar M, Amalraj L, Mehalingam P (2012) Ethnomedicinal plants used to treat skin diseases in Pothigai hills of Western Ghats, Tirunelveli district, Tamil Nadu, India. J Biosci Res 3: 112-121
  104. Takeda T, Narukawa Y, Hada N (1999) Studies on the constituents of Leonotis nepetaefolia. Chemical and pharmaceutical bulletin 47(2): 284-286
    CrossRef
  105. Tany RF, Saha AK (2017) A study on stress and anxiety in relation to asthma. Journal of Psychosocial Research 12(1): 117
  106. Tidke PC, Chambhare N, Umekar MJ, Lohiya RT (2021) Pharmacological Activity, Chemical Composition and Medical Importance of Leonotis nepetifolia R. Br.;. J Altern Complement Med 15(4): 29-43
  107. Tiwari R, Latheef SK, Ahmed I, Iqbal H, Bule MH, Dhama K, Samad HA, Karthik K, Alagawany M, El-Hack ME (2018) Herbal immunomodulators-a remedial panacea for designing and developing effective drugs and medicines: current scenario and future prospects. Curr Drug Metab 19(3): 264-301
    Pubmed CrossRef
  108. Tiwari VJ (2019) Ethnopharmacology of Leonotis nepetifolia (L.) R. Br., Lamiaceae, used to cure Jaundice and Liver Disorders by Baiga Tribe of Mandla District of Madhya Pradesh. Research Journal of Pharmacognosy and Phytochemistry 11(1): 1-7
  109. Tugume P, Nambejja C, Nyakoojo C, Kamatenesi-Mugisha M (2019) Medicinal plant species used in the treatment of skin diseases in Katabi Subcounty, Wakiso District, Uganda. Ethnobotany Research and Applications 18: 1-17
    CrossRef
  110. Ueda F, Iizuka K, Tago K, Narukawa Y, Kiuchi F, Kasahara T, Tamura H, Funakoshi-Tago M (2015) Nepetaefuran and leonotinin isolated from Leonotis nepetaefolia R. Br. potently inhibit the LPS signaling pathway by suppressing the transactivation of NF-κB. International immunopharmacology 28(2): 967-97
    Pubmed CrossRef
  111. Van Andel T, Van’t Klooster C (2007) Medicinal plant use by surinamese immigrants in Amsterdam, the Netherlands. Travelling cultures and plants:. The ethnobiology and ethnopharmacy of migrations 7: 122-144
  112. Vasuki K, Senthamarai R, Sudhakar P (2016) Investigation of antioxidant potential of an ethanolic extract of whole plant of Leonotis nepetifolia (L). R. Br. ejpmr 3: 219-222
  113. Veerabadran U, Venkatraman A, Souprayane A, Narayanasamy M, Perumal D, Elumalai S, Sivalingam S, Devaraj V, Perumal A (2013) Evaluation of antioxidant potential of leaves of Leonotis nepetifolia and its inhibitory effect on MCF7 and Hep2 cancer cell lines. Asian Pacific Journal of Tropical Disease 3(2): 103-110
    KoreaMed CrossRef
  114. Wagh VV (2016) Preliminary study on Ethno-medicinal plants used for treating malarial fever in Pilibhit Tiger Reserve, Uttar Pradesh, India. Int J Bioassays 5(7): 4672-4676
    CrossRef


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