Antiviral activities of some Ethiopian medicinal plants used for the treatment of dermatological disorders

https://doi.org/10.1016/j.jep.2005.08.071Get rights and content

Abstract

Acokanthera schimperi (Apocynaceae), Euclea schimperi (Ebenaceae), Inula confertiflora (Asteraceae), Melilotus elegans (Leguminosae), and Plumbago zeylanica (Plumbaginaceae), are some of the medicinal plants used in Ethiopia for treatment of various skin disorders. In this study, the antiviral activities of the 80% methanolic extracts of these plants have been examined against coxsackievirus B3 (CVB3), influenza A virus and herpes simplex virus type1 Kupka (HSV-1) using cytopathic effect (CPE) inhibitory assays in HeLa, MDCK, and GMK cells, respectively. In parallel, the cytotoxicity was quantified using a crystal violet uptake assay. The antiviral activity of the most active compound was confirmed with plaque reduction assays. The results revealed that the extracts of Acokanthera schimperi and Euclea schimperi showed antiviral activity against all three tested viruses albeit with unequal efficacy. Whereas the Acokanthera schimperi extract exhibited the strongest activity against CVB3, the extract of Euclea schimperi inhibited influenzavirus A replication most effectively. A weak anti-influenzavirus A activity was also exhibited by the other plant extracts tested. In addition, CVB3 was inhibited by the extracts of Plumbago zeylanica and HSV-1 by Inula confertiflora. Thus, the extracts of these plants, particularly those of Acokanthera schimperi, Euclea schimperi and Inula confertiflora which showed activity against CVB3 and HSV-1 support their traditional use in the treatment of skin diseases of viral origin.

Introduction

Infectious skin diseases including those of viral origin are highly prevalent throughout the developing countries (Paige and Leigh, 1998). Literature survey reveals high prevalence of skin diseases in Ethiopia (Dagnew and Gunther, 1990, Dagnew and Erwin, 1991, Figueroa et al., 1996, Figueroa et al., 1998, Hiletework, 1998, Sheibeshi, 2000), the situation being exasperated by the high prevalence of the pandemic HIV/AIDS. Infection with HIV may be associated with a large number of clinical manifestations. Cutaneous diseases, caused by herpes simplex virus (HSV-1 and HSV-2), are among the most prevalent (Mayanja et al., 1999, Jing and Ismail, 1999, Ippolito et al., 2000, Jensen et al., 2000, Kumarasamy et al., 2000, Muhammad et al., 2003). As HIV disease progresses, cutaneous and mucosal complications become more severe and occur in up to 92% of HIV-infected individuals (Tappers et al., 1995, Darley, 1998). Medications available for systemic treatment of HSV are acyclovir, famciclovir and valacyclovir. Acyclovir and penciclovir are available for topical use (Wyatt et al., 2001). In clinical practice, treatment of primary HSV infections, while relieving symptoms and reducing the duration of viral shedding, does not prevent recurrences (Pielop et al., 2000, Strand et al., 2002). Moreover, resistance to acyclovir has been reported in immuno-compromised patients (Pottage and Kessler, 1995).

Hand, foot, and mouth syndrome is another virus-induced skin disease. It is caused by enteroviruses, for instance coxsackie B viruses (Melnick, 1990). To date, effective treatment is not available for these infections. Patients are treated only symptomatically.

There are several medicinal plants used traditionally or as complementary/alternative medicines to treat skin disorders. The use of such medicinal plants for the treatment of skin disorders arguably has been based largely on historical/anecdotal evidence (Brown and Dattner, 1998, Mantle et al., 2001). However, a few extracts of medicinal plants that have been reported to possess in vitro anti-HSV-1 activity include for instance tea tree oil of Melaleuca alternifolia (Schnitzler et al., 2001); garlic (Allium sativum) extract (Weber et al., 1992); the flavonoid apigenin of chamomile (Matricaria recutita L) (Mucsi et al., 1992) and Hamamelis virginiana Bark (Erdelmeier et al., 1996).

Based on long time experience, various plants are used in Africa to treat skin diseases. The information about these plants is provided by ethnomedicine. In Ethiopia, Acokanthera schimperi (Apocynaceae), Euclea schimperi (Ebenaceae), Inula confertiflora (Asteraceae), Melilotus elegans Salzm. ex Ser. (syn. Melilotus abyssinica Bak.) (Leguminosae), and Plumbago zeylanica (Plumbaginaceae) are some of the medicinal plants that are used to treat skin disorders. Several parts of Acokanthera schimperi and the leaves of Euclea schimperi are used for the treatment of scabies, leprosy, Tinea capitis, wound, eczema, acne, warts, rheumatic pain and elephantiasis (Gelahun, 1989, Abebe and Ayehu, 1993). Inula confertiflora finds application in the treatment of herpes and fungal infections (Tinea capitis and Tinea corporis), wound and eczematous lesions (Messele, 2004) while the ointments made from the leaves of Melilotus elegans are topically used against haemorrhoids, mouth inflammation and lacerated wounds (Asres et al., 2000). The roots of Plumbago zeylanica are widely used for the treatment of wound, eczema, scabies, leishmania, leprosy and rheumatoid pain (Abebe and Ayehu, 1993); and plumbagin isolated from this plant has been shown to possess broad antibacterial and antifungal activities (Mohana and Purushothoman, 1980, Duraga et al., 1990, Ahmad et al., 1998).

Based on this knowledge we expected that materials from these plants possibly represent a reservoir of pharmacologically active substances and drugs. To prove this hypothesis and in order to rationalize their traditional use in the treatment of skin disorders of viral origin, the activities of the 80% methanolic extracts of the above mentioned Ethiopian medicinal plants against the enterovirus CVB3 (a non-enveloped single positive-stranded RNA virus) and herpes simplex virus type 1 (an enveloped double-stranded DNA virus) were studied. Additionally, influenza A virus (an enveloped single negative-stranded RNA virus) was included in these studies.

Section snippets

Plant materials

The leaves of Acokanthera schimperi, Euclea schimperi, Inula confertiflora and Melilotus elegans were collected in October 2002, from around Debre-Zeit (50 km South of Addis Ababa); Gurage Zone, Aklil Woreda (some 150 km west of Addis Ababa); Entoto area (Northern Addis Ababa); and in and around Addis Ababa, respectively. The roots of Plumbago zeylanica were collected during the same time from Washa Michael (near Filiklik town), Abay Gorge about 200 km west of Addis Ababa. Sample specimens were

Extraction

The leaves of Acokanthera schimperi, Euclea schimperi, Inula confertiflora and Melilotus elegans were defatted before extraction with 80% methanol. But, the roots of Plumbago zeylanica were extracted directly without defatting, since reports indicate that the active principle of Plumbago zeylanica, plumbagin is soluble in petroleum ether (Azad et al., 1981, Kamal and Leslie, 1988). N-hexane and chloroform extracts have also resulted in the isolation of naphthoquinone derivatives including

Discussion

The results of the present investigations provide further evidence of the potential of African plants for the therapeutic applications, in this case skin disorders caused by viruses. The five plants investigated originated from Ethiopia and are traditionally employed for the treatment of skin disorders of different origin. The selection of samples on the basis of ethnomedical considerations gave a high hit-rate. Four of the five extracts have now been proven to possess significant antiviral

Acknowledgements

The financial support of AvH Foundation to TGM for research visit to Martin-Luther-University and University of Tübingen is greatly acknowledged. We thank S. Linde and V. Güntzschel for excellent technical assistance.

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