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Virus Research 131 (2008) 111–120
Antiviral potentials of medicinal plants
Muhammad Mukhtar a,d , Mohammad Arshad b , Mahmood Ahmad b , Roger J. Pomerantz c , Brian Wigdahl d , Zahida Parveen e,∗
University of Arid Agriculture Rawalpindi, Murree Road,Rawalpindi 46300, Pakistan b The Islamia University of Bahawalpur, Pakistan c Tibotec Inc., Yardley, PA, USA d Department of Microbiology and Immunology, Institute for Molecular Medicine and Infectious Diseases, Drexel University College of Medicine, Philadelphia, PA 19102, USA e Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA Received 25 April 2007; received in revised form 6 September 2007; accepted 7 September 2007 Available online 5 November 2007
Abstract Medicinal plants have been widely used to treat a variety of infectious and non-infectious ailments. According to one estimate, 25% of the commonly used medicines contain compounds isolated from plants. Several plants could offer a rich reserve for drug discovery of infectious diseases, particularly in an era when the latest separation techniques are available on one hand, and the human population is challenged by a number of emerging infectious diseases on the other hand. Among several other ailments, viral infections, particularly infections associated with human immunodeﬁciency virus type 1 (HIV-1) and 2 (HIV-2), and newly emerging infectious viruses have challenged mankind survival. Of importance, a variety of medicinal plants have shown promise to treat a number of viral infections, and some of them possess broad-spectrum antiviral activity. In the past, exploration into the antiviral activity of various promising medicinal plants was limited due to: (a) highly infectious nature of viruses and (b) lack of appropriate separation techniques for the identiﬁcation of antiviral components from plants. Development of vector-based strategies, in which non-infectious molecular clone of a virus could be used for antiviral screening purposes, and advancement in separation technologies offers promise for medicinal plants usage in modern drug discovery. This article describes potential antiviral properties of medicinal plants against a diverse group of viruses, and suggests screening the potential of plants possessing broad-spectrum antiviral effects against emerging viral infections. © 2007 Elsevier B.V. All rights reserved.
Keywords: Medicinal plants; Traditional medicine; Viral infections; Antivirals
1. 2. 3. 4. 5. 6. 7. 8. 9. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HIV/AIDS and medicinal plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Human herpesviruses and medicinal plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Anti-inﬂuenza virus activity of medicinal plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Medicinal plants in viral hepatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Medicinal plants in emerging viral infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Medicinal plants in miscellaneous viral infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Isolation and characterization of plant components exhibiting medicinal characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Future directions in antiviral potentials of medicinal plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 112 115 115 116 116 116 117 117 118 118
Corresponding author. Tel.: +1 215 503 9097; fax: +1 215 923 1956. E-mail address: email@example.com (Z. Parveen).
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Marburg. conﬁrming antiviral effects association with the immunostimulatory properties (Webster et al. Kwon et al.. (Plantaginaceae) commonly used plants as folk medicine in Taiwan for the treatment of infectious diseases.) are indicators of cell-mediated immune response modulation (Chiang et al.. The root extracts of medicinal plant Heracleum maximum Bartr. and limited efforts have been directed toward the identiﬁcation of active natural ingredient exhibiting antiviral effects. The molecular mechanisms associated with the antiviral effects of plant extracts may vary among different viruses.. healthcare individuals should be very cautious in practicing plants/phytochemicals medicinal usage in AIDS afﬂicted individuals. Moreover. (ii) Pandanin.. a lectin isolated from the saline extract of the leaves of Pandanus amaryllifolius Roxb. Particularly herpes simplex virus type 2 (HSV-2) (Debiaggi et al. however. Another major interest in medicinal plants is efforts of the Canadian AIDS Treatment Information Exchange (CATIE). asiatica Linn. Mukhtar et al. Sambucol. 1952).. Besides immunomodulatory effect. exhibited lymphocyte proliferation and secretion of interferon-gamma (IFN. 2004). HIV/AIDS and medicinal plants The ﬁrst International Conference on Traditional Medicine and AIDS held in Dakar. the potentials of plant extract to boost inherent antiviral defense of human body which involves an intricate immune system might utilize common pathways. England) to screen 288 plants for anti-inﬂuenza activity (Chantrill et al. however.. 2005). HIV. India. suggesting the presence of broadspectrum antiviral phytochemicals in various parts of the plants (Buckwold et al. The most important recommendation of this conference was an HIV/AIDS Research Initiative on Traditional Healthcare in Africa (HARITHAF). 2006) have challenged the modern drug discovery practices. a number of studies have explored immunostimulatory properties of plant extracts having antiviral properties (Webster et al. Traditional Medicine and Local Communities in Africa for the ﬁrst time placed the role of traditional medicine and HIV/AIDS on the international biodiversity agenda. organized by the Association for the Promotion of Traditional Medicine (PROMETRA) generated considerable support for the usage of medicinal plants among HIV-infected individuals. parallel sessions of The Fifth Conference of Parties (COP-5) to the Convention on Biological Diversity and the International Conference on Medicinal Plants. 2004).. However. HIV (Asres and Bucar. Introduction The history of medicinal plants dates back to the origin of human civilization on earth. The CATIE has prepared a list of medicinal plants showing potential beneﬁcial effects for HIV-infected individuals (Table 2) (2005b). hepatitis B virus (HBV) (Huang et al.. The Natural Health Product Regulations of Canada promulgated in January 2004 is an important step toward modernization of plant-based product usage in healthcare. TNF-alpha. (iii) crude extract of hop showed antiviral effect against a diverse group of viruses. stimulated Interleukin 6 (IL-6) production in the macrophage activation assay. Thailand and a number of African countries. 1999). 2005) were strongly inhibited by various plants extracts. The CATIE’s “Practical Guide to Herbal Therapies for People Living with HIV” is very informative document. Later studies have reported the inhibitory effects of medicinal plants extracts on the replication of several viruses.. ﬁrst recognized interest in their development as antiviral agent is the efforts of the Boots drug company (Nottingham. Moreover. 2003. 2002). inﬂuenza. 2005). (Umbelliferae) which possess antiviral effects besides antifungal and antibacterial properties. This regulation encourages usage of modern technology and evidence-based scientiﬁc support toward promoting medicinal plants and the associated products (Siow et al. 2006). 2005. 1988). 2006. detailing potential role of medicinal plants in the lives of HIV-infected individuals.112 M.. IL-6. However. showed antiviral effect against HSV-1 and inﬂuenza virus strain H1N1 (Ooi et al. / Virus Research 131 (2008) 111–120 1. 2003).. 2001). Among several such observations few are: (i) an extract of the Trifollium species Secomet-V exhibited antiviral effect against a number of infectious viruses such as human papillomavirus. HIV/AIDS was selected as priority for future research and development in the area of medicinal plants in Africa. which is effective against various strains of inﬂuenza had shown to boost immune responses by secreting inﬂammatory cytokines (IL-1 beta. Sri Lanka. This could be associated with a single phytochemical...) at low concentrations. and P. Along with similar lines. and IL-8) (Barak et al. Developed countries are also turning to encourage the usage of plant-based natural medicinal product in their healthcare systems.. Both lymphocyte proliferation activity and induced secretion of interferon-gamma (IFN. and suggested the decade 2000–2010 as “Decade for the Development of African Traditional Medicine” (2000).. as the information collected by the CATIE . Furthermore. a product isolated from Sambucus nigra L. and deem a very careful look toward exploring natural antiviral components of medicinal plants. and emerging viral infections associated with poxvirus and severe acute respiratory syndrome (SARS) virus (Kotwal et al. Vermani and Garg. 2. Based on the recommendations of this meeting. Tolo et al.. Japan. Plantago major Linn. In recent past. their wide usage had been limited to China. 2006). A detailed review has previously described national activities around the globe relevant to medicinal plants usage priorities (Hoareau and DaSilva. HBV and HCV (Kotwal et al. an organization involved in improving the health and quality of life for people living with HIV/AIDS in Canada. Most of these studies have utilized either water soluble or alcoholic extracts of medicinal plants. recent studies showing antiviral potential of plant extracts against viral strains resistant to conventional antiviral agents (Serkedjieva. entrusted with the responsibility of developing controlled clinical protocols for evaluating the safety and efﬁcacy of potential phytomedicines for HIV/AIDS. 1979). Medicinal plants have been used throughout the world. Senegal in the year 1999. Several of these may have been used to treat viral infections in the past. another intriguing ﬁnding is the broad-spectrum antiviral nature of plant extracts (Pompei et al. or a number of different plant constituents. 2005) (Table 1). Pakistan.
(2005) Zuo et al. cyanovirin N (CV-N). efforts in the past to ﬁnd an effective cure for HIV infection has met with disappointing results. leaves. Furthermore. isolated from Lycoris radiate possesses anti-SARS-CoV Inhibits HIV replication both in vitro and in vivo Inhibits acute infection and cell-to-cell transmission of HIV-1 Leaves extract of Trichilia glabra inhibits VSV Inhibition of human adenovirus type 1 and coxsackievirus B1 in a dose-dependent manner The aqueous extract of neem leaves inhibited DEN-2 both in vitro and in vivo Reference Tolo et al. Witvrouw et al. Elderberry extract (Pantev et al. roots. The CV-N possesses broad-spectrum antiviral activity besides inhibiting HIV-1 infection (Boyd et al. CXCR4. respectively A medicinal plant reducing the infectivity of various inﬂuenza virus strains in vitro and in vivo A randomized.M. 2005. (2007) 113 Inﬂuenza virus Geranium sanguineum L. & Thonn. HAART can only control HIV infection among individuals continuously on therapeutic regimen and withdrawal of medication leads to reemergence of the diseases. (2004) Hepatitis B virus Boehmeria nivea L. CCR5. The plant kingdom is highly diverse and ranges from unicellular microscopic plants to long-lived huge trees. as well as. Further exploration and identiﬁcation of natural products for controlling HIV and associated infections is necessary due to several reasons. & Zucc. 1. ﬂowers. Polygonum cuspidatum Sieb. (2003) Parida et al. (2002) Vesicular stomatitis virus (VSV) Human adenovirus type 1 Dengue virus type-2 (DEN-2) are anecdotal and lack scientiﬁc validity. (Neem) Notka et al.6-penta-O-galloyl-beta-d-glucoside isolated from Saxifraga melanocentra Both plants extract inhibited poliovirus replication. (2004) Lee-Huang et al. development of vaccine for HIV pandemic seems a far-fetched dream. The antiviral activity of CV-N has been dissected at molecular levels and involves highly speciﬁc interactions with the viral envelope glycoprotein gp120 (Barrientos et al. (2006) and Serkedjieva (1997) Zakay-Rones et al. The CATIE’s “Practical Guide to Herbal Therapies for People Living with HIV” is a good start highlighting the potentials of phytochemicals extracted from plants. Mukhtar et al. (2004) Yamai et al. The viral envelope plays a major role in the infectivity of permissive cells and mediates interactions with permissive cells CD4 receptors in concert with chemokine receptors. double-blinded placebo-controlled study revealed that elderberry extract seems to offer an efﬁcient.2. Moreover.. (2005) Hepatitis C virus (HCV) Poliovirus Felipe et al. (2006) Viral haemorrhagic septicaemia virus (VHSV) Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) Human immunodeﬁciency virus Stryphnodendron adstringens Olea europaea L. none of these strategies have led to cure. & Irmsch. blocked the synthesis of viral antigens in infected cell cultures Leaf extract inhibited viral replication Lycorine. Esser et al.3. 2003. (2005) Phyllanthus amarus Schum. (2003) Cella et al. First. There are also examples of antiviral properties of plants. Lycoris radiate Micol et al. Appropriate clinical trials are also necessary for validating medicinal usage of plants among humans. there is lack of qualiﬁed personnel in the ﬁeld of medicinal plants. (2006) Yang et al. (2006) Chang et al. 1997) and is on the list of potentially emerging antiviral compounds (De Clercq. Antiviral effect A medicinal plant exhibiting strong anti-HSV 1. or phytochemically screened products based on the properties of newly identiﬁed phytocomponents. Current knowledge relevant to antiviral properties of medicinal plants is based on subjective information. Phyllanthus urinaria L.4. safe and cost-effective treatment for inﬂuenza A root extract of Boehmeria nivea reduced HBV production in an in vitro and in vivo model Inhibits hepatitis B virus in a stable HBV-producing cell line A compound namely 1. Black soybean extract Azadirachta indica Juss.. / Virus Research 131 (2008) 111–120 Table 1 Partial list of viruses inhibited by medicinal plants Virus Herpes simplex virus (HSV) Medicinal plant used Carissa edulis Vahl. The most effective therapeutic regimen for HIV-infected individuals is highly active antiretroviral therapy (HAART) which is a combination of protease inhibitors and nucleoside or non-nucleoside reverse transcriptase inhibitors. One such example is a potential antiviral compound. an 11-kDa protein isolated from the cyanobacterium Nostoc ellipsosporum. Screening of each and every plant or their individual parts (stem. however. and 2 activities both in vitro and in vivo 1346TOGDG and geraniin isolated from Phyllanthus urinaria inhibited HSV-1 and HSV-2. Olive leaf extract (OLE) Trichilia glabra L.. Huang et al.. Saxifraga melanocentra Engl. 1999). (2005) Li et al. which . bark) for the identiﬁcation of antiviral components is impossible. 2005). There is also a class of antiviral compounds known as HIV entry inhibitors. Second. based on HIV pathogenesis efforts have been made to target every step of viral life cycle starting from entry to viral morphogenesis as shown in Fig. Guazuma ulmifolia Lam.
a drug extracted from Andrographis paniculata increased CD4+ counts and 30% decrease in viral load was recorded after 9 weeks in preliminary trials Have been prescribed by Ayurvedic practitioners to rejuvenate the immune system of HIV-positive people.. HIV people use it for preventing nausea and stimulating appetite In vitro antiviral (against HIV) and antioxidant properties have been reported Psyllium ﬁber bars are useful for diarrhea. Besides CV-N. Glycyrrhiza glabra L. 1998. Canadian federal government has a system to grant the legal rights to grow and possess. etc. certain products isolated from seeds may prevent HIV-associated memory loss A tonic herb which improves cell-mediated immune system usually ravaged among HIV-infected individuals. A recent study compared various plants and their individual parts (stem. also reduced immunodeﬁciency-associated diarrhea with immune function improvement A small study showed an increase in CD4+ counts of individuals taking Uncaria tomentosa. Antioxidant and immunomodulatory properties have also been described Amerliorate conditions associated with HIV infection such as fungal infections (thrush) and parasitic infections (cryptosporidium) May be beneﬁcial for nausea associated with antiretroviral treatment Ingestion of Gingko biloba seeds itself is toxic. Panax ginseng C.f. a complex sugar extracted from Aloe vera used for retroviral infection (a) Antiviral effect through immunomodulation.114 M.. Zingiber ofﬁcinale Roscoe. Zhang et al. John’s Wort Buxus sempervirens L. Astragalus Atractylodes Astragalus membranaceus Bunge. Ashwagandha leaves Withania somnifera (L. the immune cells involved in controlling microorganisms Mild antiretroviral effects Antiretroviral effects associated with exposure to light (photosensitive antiretroviral component). (b) AndroVir. Meyer. (b) Acemannan.) Coult. (Siberian) Hydrastis canadensis L. 2004. leaves. Berberine present in Hydrastis Canadensis has potential of controlling diarrhea and weight loss among HIV-infected individuals Due to anticancer properties may be beneﬁcial for HIV-associated Kaposi sarcoma In vitro studies shows that Hyssopus ofﬁcinalis inhibits the replication of HIV without any toxicities In vitro antiviral properties against HIV and HSV Glycyrrhizin present in Glycyrrhiza glabra have immunostimulatory properties and inhibit viral production Both Lomatium dissectum and Lomatium suksdorﬁi inhibit HIV in vitro Andrographis Andrographis paniculata (Burm. Atractylodes macrocephala Koidz. SPV30 (boxwood extract) St. Garlic Ginger Gingko (seeds) Ginseng (roots) Allium sativum L. & Maxim. Contraindicated during pregnancy An alkaloid. Sanguinaria canadensis Asparagus racemosus Willd. Inactivate conventional antiretrovirals and as such contraindicated for HIV patients on other medications Controls HIV-associated thrush (fungal infections) Information based on CATIE’s “Practical Guide to Herbal Therapies for People Living with HIV”. (North American). / Virus Research 131 (2008) 111–120 Table 2 Plants and their products used among HIV-infected individualsa Common name Aloe Scientiﬁc name Aloe vera Activity/comments (a) Jelly-like substance found in the leaves may be used to treat skin problems associated with HIV and anti-HIV drugs.) Mathias & Constance) Lomatium suksdorﬁi (Wats... 2006). another natural product originating from plant source interacts with chemokine receptors and inhibits entry of HIV (Kitamura et al. Lomatium dissectum (Nutt. interact either with viral envelope or host cell receptors mediating viral entry.) Maxim. a side effect of protease inhibitors therapy among HIV-infected individuals Have been used for Pneumocystis carinii pneumonia (PCP) usually encountered by HIV-infected individuals Immunostimulant. Wang et al. animal studies have conﬁrmed immunostimulatory properties A bone marrow stimulant and one of the ﬁrst herb showing anti-HIV activity by the Chinese medicine practitioners HIV-positive people have used roots of Atracylodes for improving body weight. Plantago ovata Forssk. In .) Dunal. Mukhtar et al. Now a days effort have been directed to characterize the anti-HIV activity of medicinal plants at molecular level. Cannabis sativa L. Panax quinquefolium L. Hypericum perforatum L.. roots. Gingko biloba L. (Asian). Hyssopus ofﬁcinalis L. Chelidonium majus L. Baicalin. Cat’s claw (inner bark) Uncaria tomentosa Willd. & Rose. Goldenseal (roots) Greater Celandine (ﬂower) Hyssop (leaves and ﬂowers) Lemon balm Licorice (roots) Lomatium Marijuana Olive leaf Psyllium (seed and husk of plant) Sanguinaria Shatvari Olea europaea L. muscle strength. however. Tea tree oil a Melaleuca alternifolia The production and sale of marijuana is illegal.) Nees. the two essential enzymes in HIV infection (Bessong et al.) in inhibiting viral reverse transcriptase (RT) and integrase. 1991). however. Li et al. in vivo studies showed that Asparagus racemosus stimulate macrophages. Medically. 2000. Melissa ofﬁcinalis L. Eleutherococcus senticosus (Rupr.
inhibited HSV type 1 (HSV-1) (Bedows and Hatﬁeld. Anti-inﬂuenza virus activity of medicinal plants The quest for inﬂuenza virus natural inhibitors is very ancient. isolated from the acetone extract of another plant Phyllanthus urinaria. Besides aqueous extracts. i. HHV-6. 2006). aqueous extract of plant material has been used to treat HSVassociated infections. Medicinal plants have also shown inhibitory effects on viral protease (PR).. In the past. Ongoing efforts are crucial toward further development of previously characterized protease inhibitors and identiﬁcation of new compounds with such activity. Human herpesviruses and medicinal plants Several members of the human herpesviruses (HHV) family are causative agent for human diseases. As RT plays a major role in controlling viral infectivity and replication. Prajoubklang et al. 3. HAART. in the past. Studies in the past and recent literature suggest that a variety of natural products isolated from several plants inhibit inﬂuenza virus both in vitro (Mothana et al. HIV life cycle and potential antiviral targets. several scientiﬁc efforts have been directed toward identifying phytochemicals capable of inhibiting inﬂuenza virus (Cochran et al. 2006). Woradulayapinij et al.. An intriguing observation is the presence of anti-inﬂuenza activity in a wide variety of phytochemicals. several reports have linked medicinal plants capability to inhibit RT activity an indirect measurement of anti-HIV effect (Fu et al. The other members of herpesviruses causing different illnesses are: HHV3 (varicella zoster virus). polyphenols. a medicinal plant locally growing in Kenya. There has always been a quest for antiviral which can overcome resistant strains of viruses or suppress emergence of viral resistance.e. comparing organic solvents and aqueous fractions of various medicinal plants. In the past century.M. such as triterpene derivatives from a number of medicinal plants have shown inhibitory effects on PR (Huang and Chen. 2006. 4. such as alkaloids. Prahoveanu et al. The majority of HHV infections are associated with HSV-1 and HSV-2. 2006).. the alcoholic. 2005). Based on available information one can easily speculate about the presence of natural antiviral compounds effective against resistant strains of viruses. / Virus Research 131 (2008) 111–120 115 Fig.. None of the six potential antiviral medicinal plants tested in this study inhibited integration step. Of importance. Two compounds namely geraniin and 1. HHV-4 (Epstein Barr virus). 1986). 2005) and in vivo (Ivanova et al. HSV. organic solvents extracts of various plants have also shown anti-HSV activity. Naturally occurring RT and protease inhibitors in various medicinal plants also offer a reserve of unexplored antiviral compounds. 2005. 2005. Kostova. One such precedent is an aqueous extract from the roots of Carissa edulis (Forssk. 1. we will be able to see an effective phytochemical for controlling the inﬂuenza virus. 1978). particularly HIV-infected individuals. phytochemicals.. the most favorable therapeutic regimen for treating HIV-infected individuals also contain protease inhibitors as part of the combination drugs cocktail. n-butanol fraction of the Bridelia micrantha (Hochst) showed highest anti-RT activity. Moreover. an enzyme essential for proteolytic processing of polyprotein precursor into proteins essential for the assembly of viral particles.. This study also identiﬁed a potential anti-RT component of a medicinal plant which requires further investigation.. 2006. Podophyllotoxin. 2002. ﬂavonoids. For example. Mukhtar et al. HHV-7 and HHV-8. saponins (Wang et al.. 1982).. Hussein et al.) Vahl (Apocynaceae).6-tetra-O-galloyl-betad-glucose (1346TOGDG). Park et al. HSV infections are usually serious problems among immunocompromised individuals. 2005. 1966.4.. Pantev et al. It is being hoped that in near future. HHV-5 (Cytomegalovirus). isolated from the aqueous extract of Podophyllum peltatum L. 2006. In the past. May and Willuhn. Yu et al. showing remarkable anti-HSV activity in vitro and in vivo for both wild type and resistant strains of HSV (Tolo et al. The phytochemical. glucosides. 2007).. also suppressed HSV-2 and HSV-1 (Yang et al. 1999. suggesting varied nature of antivirals present in medicinal plants.. . development of resistant herpes strains refractory to conventional antiviral drugs is also a major issue.3. most of the medicinal plants have been explored against a single member of herpes family. RT inhibitors are already in the armamentarium of anti-HIV agents.. 2006..
6. Q. Based on previous observations. Evaluation of previously completed 13 randomized trials analysis included in this study showed that only four have appropriate methodologies. Microarray analyses revealed the anti-HBV activity of ethanolic extract of another member of Phyllanthus (P. C. Various herbal products adverse events were also summarized in this information collection report (Liu et al. however. B. 1996. P. screening of antiviral compounds has been snagged due to the lack of representative smaller animal model. respectively. Further studies compared antiviral activity of P. 1995). The methanolic extracts of Acacia nilotica L.. like Silybin. MEDLINE. 2003).) showed its inhibitory effect on HBV polymerase activity and mRNA transcription due to interactions with HBV enhancer I and C/EBP alpha and beta transcription factors (Lee et al. Such reports strongly suggest appropriate vigilance programs as well as involvement of international regulatory agencies for assessing the beneﬁts of herbal medicine... 1999). A number of plants previously shown to possess broad-spectrum antiviral effects could be screened for newly emerging/resistant viral strains. 2006). A number of Chinese herbal mix such as Bing Gan Tang. Trachyspermum ammi L. co-fermentation of both these medicinal plant for the development of antiviral broth showed superior antiviral effect compared with simple mixing (Li et al. few herbs/phytochemicals used in clinical trials have anti-HCV activity. nanus.. A study reviewed the beneﬁcial and adverse effects of herbal preparations used for the treatment of viral hepatitis in the Cochrane Collaboration. various members of this plant family were screened for their antiviral effects in DHBV model. which showed a signiﬁcant reduction of serum aspartate aminotransferase (AST) and gamma glutamyltranspeptidase levels and HCV clearance.. Clinical studies were also designed to compare anti-hepatitis B effects for different species of Phyllanthus... maderaspatensis (Munshi et al. Initial ﬁndings revealed that Phyllanthus amarus has no signiﬁcant inhibitory effect on DHBV DNA replication in vivo (Niu et al. polysterols. Ardisia chinensis. Willd ex Delile. For example. P. 2006). The identiﬁcation of anti-HBV potentials of Oenanthe javanica Blume DC ﬂavones (OjF). Although P. EMBASE. another member of the Phyllanthus genus of plants showed strong inhibitory effect in controlling DHBV in primary cell culture model (Lam et al. Data from manual searches for ﬁve Chinese and one Japanese journals were also included besides information from randomized clinical trials (Liu et al. Quercus infectoria. and Oxymatrine. 1990). in the case of HBV infection in humans. Traditional medicine for viral hepatitis has mainly focused on plants belonging to the genus Phyllanthus of the Euphorbiaceae family. Moreover. and BIOSIS databases. The DHBV system has been used for screening anti-HBV effect of various medicinal plants. 2000).) (Wang et al. amarus and P.. liquid fermentation broth of Ganoderma lucidum on supplementation with aqueous extract of Radix Sophorae ﬂavescentis (Chinese herbal medicine) showed strong anti-hepatitis B virus activity in vitro and in vivo. Although exposure to any of these viruses leads to acute infection.e. showed potentials to inhibit HCV (Hussein et al. maderas (Munshi et al. 1993b) in DHBV model and concluded that these medicinal plants do not have any therapeutic potential against HBV in humans as previously thought. 2003).2. Such controversial data need further investigation at molecular level to validate initial clinical data in the DHBV model. a bioactive component of liquorice (Glycyrrhiza uralensis Fisch). i. 7. showed strong anti-SARS-CoV activity (Li et al.. that suggested anti-HBV effect of Phyllanthus species. For example screening of 56 different Chinese medicinal herbs led to the identiﬁcation of two potentials anti-DHBV plant extracts... 2006). 2005). i. and lycorine isolated from Lycoris radiata L. Mukhtar et al.. duck hepatitis B virus (DHBV) model has served as an excellent screening system (Niu et al. amarus (L. D and E. One such example is Glycyrrhizin. type B. and Pithecellobium clypearia (Leung et al. P. Besides resolving initial observation relevant to therapeutic development of Phyllanthus species plants. and D are unique in causing chronic infection.15 cells and reducing DHBV-DNA levels in the HBV-infected duck model is also credited to this valuable model (Wang et al.) and P. Patrick. glycyrrhizin. Medicinal plants in emerging viral infections Emerging viral infections are posing a major threat to the mankind. Yi Zhu decoction. niruri (L. Medicinal plants exhibiting broad antiviral effects could be brought into the antiviral discovery programs for such infection.. as a strong inhibitor of HBsAg and HBeAg secretion (involved in viral pathogenesis) in 2. For viral hepatitis such combination therapies have also been tried. Disappointingly.). However. amarus (L. Embelia schimperi. Furthermore.. 2005). Screening programs aimed at the identiﬁcation of anti-HCV medicinal plants are ongoing. infectoria and Syzygium aromaticum L. / Virus Research 131 (2008) 111–120 5. Usually.. Hepatitis C is another member of the viruses causing viral hepatitis. C. 2003. particularly due to the prevalence of infection in the resource poor countries and lack of good vaccine. Molecular studies on antiviral potentials of P. Boswellia carterii. Medicinal plants in miscellaneous viral infections A variety of herbal (medicinal) preparations have shown potentials for inhibiting viruses causing serious infections . and Yi Er Gan Tang individually or in combination with antivirals showed beneﬁcial effects on clearing HCV RNA and normalizing serum alanine aminotransferase (ALT). Ott et al.. a number of phytochemical products such as catechin. Medicinal plants in viral hepatitis Viral hepatitis or inﬂammation of the liver is caused by a number of different viruses named hepatitis A.116 M. 1990).e.. 1997). 1993a). silymarin potentials as anti-HCV agents have also been reviewed (Jassim and Naji. urinaria (L. and aqueous extracts of Piper cubeba L.. nanus) due to over expression of several genes particularly annexin 7 (Anx7) (Lam et al. 2006). DHBV model has been very helpful in identifying a number of other plants which could be potentially utilized for isolation of candidate therapeutics for appropriate clinical trials. initially used for certain other indication. Sometimes several medicinal plants are mixed together to develop a combination therapy for treating a particular ailment.
efforts are ongoing to replace traditional methodologies with modern sample preparation and extraction procedures. 2006. To further facilitate plant-based drug discovery efforts are also being directed toward standardization of methodologies which can be used to study pharmacokines/pharmacodynamics behavior of phytomedicinal products (Lin et al. Takahashi et al. Unfortunately. 2006).. respiratory syncytial virus (RSV). A few to start with could be: Plant Drug Analysis: A Thin Layer Chromatography Atlas (Wagner et al. it can be fairly concluded that medicinal plants offer a variety of anti-infectious compounds... Programs aimed at inclusion of medicinal plants into the healthcare need of the people should be sponsored in countries where plants and their products are practiced for medical needs. 2006.. 2004). 2002. There are other issues to be resolved before the translational usage of medicinal plants in the developed world. 8. In recent past. 2001).. To prove/disprove antiviral effect of any herbal preparation it is essential to molecularly dissect its effects. 80% of the World’s population fulﬁlls their healthcare needs from phytomedicinal sources (2005a). increased interest in traditional medicine has complemented quality awareness and reﬁnement in extraction methodologies and standardization of procedures for phytochemedicinal products isolation (Atta-ur-Rahman and Choudhary. i. There are several books and reviews describing standardized extraction procedures from medicinal plants. neurotropic Sindbis virus (NSV) (Paredes et al. Thanavala et al. 1998.. / Virus Research 131 (2008) 111–120 117 among humans such as measles viruses (Olila et al. Melo et al. 2005). matrix-assisted laser desorption/ionization mass spectrometry (Wu et al. One such example is the molecular study of the hot water extracts of Stevia rebaudiana L. Most of the books published in phytomedicine have mainly paid attention to classical isolation procedures. 2003.. 1985). 1994. 2005). 1994). Su et al... Due to these limitations efforts have been directed toward expressing coat proteins of different viruses which are presumed to assemble as virus-like-particles (VLP) in plants and are antigenic in nature. For example screening of the antiviral potentials of plant extracts always posed a threat of incidental infection to the workers.. Vector-based assay techniques have been very helpful in overcoming such screening hurdles. Several problems previously thought to be hurdle in the medicinal plants antiviral drug discovery program are no longer an issue. 2001) and various strains of poliovirus (Andrighetti-Frohner et al. 2001). for coun- . Similarly an alkaloid extract of Haemanthus albiﬂos bulbs inhibited RNA synthesis of HRV propagated in MA-104 cells (Husson et al. 1999).. 1996)... pressurizedliquid extraction. Very few studies have addressed this important aspect relevant to the therapeutic development of phytochemicals. Vilagines et al. Improved separation technologies offer potentials to screen medicinal plant’s anti-infectious/antiviral nature. 2004. coxsackie group of viruses (Evstropov et al.. Ma et al. Several other issues like appropriate processing of protein to be expressed in plants are important aspects to be considered. 2007) and several others. The countries having heavy usage of traditional medicine should sponsor scientiﬁc programs devoted toward modern drug discovery from phytochemicals. thus compromising the safety and efﬁcacy of phytomedicinal preparations. Modern Phytomedicine: Turning Medicinal Plants into Drugs (Ahmad et al.. To ensure high quality herbal preparations. particularly antiviral agents. 2005). which blocked entry of various infectious serotypes of HRV into the permissive cells by an anionic polysaccharide having a molecular weight of 9800 with uronic acid as a major sugar constituent (Takahashi et al. however.M. 1998). 2007) and Laboratory Handbook for the Fractionation of Natural Extracts (Houghton and Raman. 9. 2006.e. Although it will be hard to get these plant extracts approved through international regulatory agencies such as the Food and Drug Administration (FDA) of the United States of America or other equivalent European counterparts. Isolation and characterization of plant components exhibiting medicinal characteristics The very ﬁrst and basic step towards evaluating the therapeutic potential of a medicinal plant is preparation of crude cellular lysate of the plant matrix followed by extraction of various components having potential medicinal value. Since the expression of ﬁrst subunit vaccine for HBV surface antigen in 1992. In certain parts of the world crude plant extracts are used in healthcare and their efﬁcacy is well-documented without any side effects. Based on all the above information. Koprowski and Yusibov. as majority of viral vaccines are constituted of attenuated or inactivated viral particles. Classical solvent separation of phytomedicinal products is being complemented with modern techniques like microwave-assisted extraction. One such issue is the isolation of active ingredient associated with the medicinal characteristics of a particular plant. Screening programs aimed at identifying potential anti-infectious agent from medicinal plants offer a great potential in the ﬁeld of pharmaceutical developments. Sindambiwe et al. recombinant viral vectors mimicking the infection and expressing ﬁreﬂy luciferase marker gene have been widely used to screen a variety of antivirals (Esimone et al. Mukhtar et al. Ong.. As such there is an urgent need to reﬁne and further develop classical methodologies to obtain procedural consistency and highly pure plant components exhibiting medicinal value. While considering this aspect of plants for treating human viral diseases one has to be careful. Future directions in antiviral potentials of medicinal plants The importance of medicinal plants can be ascertained from the fact that according to the World Health Organization (WHO) estimates. 2001). several other different vaccine antigens have been successfully expressed in plants and their safety has been assessed in animal and humans (Glenz and Warzecha.. human rotaviruses (HRV) (Husson et al. human rhinoviruses (Glatthaar-Saalmuller et al.. A clever usage of plants is the production of vaccines and protein-based therapeutics. 2005. some of these classical procedures have limitations of reproducibility and quality. Several scientiﬁc reports suggest that plant could offer a good source for the production of pharmaceutical grade peptides/proteins (Glenz and Warzecha.. 2001)..
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