Herbal medicinal products in herpes virus diseases

In-vitro and in-vivo activity of crude herbal extracts

The search for natural antivirals was actually initiated by the Boots drug company (UK) in 1952. Since then many broad-based screening programmes have been undertaken throughout the world to evaluate the in-vitro and in-vivo antiviral activity of plant extracts and many of them revealed strong antiherpes virus activity, while some can be used as a lead for the development of antiherpes virus agents. These reviews report the in-vitro and sometimes in-vivo antiherpes virus activities of many plant extracts, mainly against HSV-1 and HSV-2.

Garlic (Allium sativum) extracts showed strong inhibitory activity against HCMV. Interestingly the intraperitoneal administration of black seed (Nigella sativa) oil to BALB/c mice strikingly inhibited HCMV in-vitro murine cytomegalovirus (CMV) titres in spleen and liver (Salem and Hossain, 2000) while the extract of Terminalia chebula not only significantly inhibited herpes simplex virus in vivo, but also the replication of HCMV in vitro and murine CMV in immunosuppressed mice.

Canadian researchers first reported the antiviral activities of grape, apple and strawberry juices against herpes simplex virus and other viruses; while leaf extract of Azadirachta indica inhibited DNA viruses. British Columbian ethnomedicines Cardamine angulata, Conocephalum conicum, Polypodium glycyrrbiza showed anti-HSV-1 activity; while strong anti-HSV activity was found with Byrsonima verbascifolia extract, a folk remedy for skin infections. The aqueous extracts of Nepeta nepetella, Dittricbia viscosa and Sanguisorba minor magnolii of the Iberian peninsula inhibited vesicular stomatitis virus (VSV) and HSV-1 at 50-125 Lig/mL; while the Nepalese ethnomedicine Nerium indicum inhibited herpes simplex virus and influenza A virus. The Chinese antipyretic and anti-inflammatory folk medicine Rheum officinale and Paeonia suffruticosa prevented herpes simplex virus attachment and penetration. Senecio ambavilla, a folk remedy of La Reunion Island, had anti-HSV-1 and anti-poliovirus activities. The extracts of Aglaia odorata, Moringa oleifera and Ventilago denticulate, folk medicines of Thailand, inhibited thymidine kinase-deficient and phosphonoacetate-resistant HSV-1 and delayed the development of skin lesions at 750 mg/kg per dose, increased the mean survival times and reduced the mortality of infected mice similar to acyclovir. The Taiwanese folk remedy Boussingaultia gracilis and Serissa japonica extract was shown to inhibit herpes simplex virus and adenoviruses (ADV) 3, 8 and 11.. Interestingly the viral adsorption, replication and transcription of HSV-1 and HSV-2 were inhibited by Ceratostigma willmattianum extract, an ethnomedicine of China, with IC50 of 29.46 and 9.2 mg/L respectively.

The extracts of Senna petersiana, a folk remedy for sexually transmitted diseases, have strong anti-HSV activity. The aqueous extract of Carissa edulis (Forssk.) Vahl (Apocynaceae) root from Kenya, significantly (100%) inhibited plaque formation in Vero E6 cells infected with 100 PFU of wild-type herpes simplex virus or resistant herpes simplex virus strains at 50 µg/mL in vitro with minimal cell cytotoxicity (CC50 480 µg/mL). The extract at an oral dose of 250 mg/kg significantly (50%) delayed the onset of herpes simplex virus infections in a murine model using Balb/C mice, cutaneously infected with wild-type or resistant strains of herpes simplex virus.

Methanol and hot-aqueous extracts of 25 different plant species, used in Yemeni traditional medicine when tested in two in-vitro viral systems using HSV-1 in Vero cells and influenza virus A in MDCK cells, showed greater activity against HSV-1 at non-cytotoxic concentrations.

In-vitro and in-vivo antiherpetic activity of compounds from herbal extracts

A list of some potential herbal extracts along with the isolated compounds having antiherpes virus activities with probable mode of action are presented in Table Important antiherpetic extracts and compounds from diverse chemical groups.

Table Important antiherpetic extracts and compounds from diverse chemical groups

Natural productSourceAntiviral activity (lg/mL)
Whole extractAglaria odorataHSV-1
Moringa oleitfera
Ventilago dentitculata
Boussingaultia gracilisHSV-1, HSV-2
Serissa japonitca
Cretastitgma willmaltianumHSV-1 (9.12, 36.5)
Senna petersitanaHSV-1
Triphasia trifoliaHSV-1, HSV-2
Artocarpus lakoocha
Millettia erythrocalyxHSV
Caritssa edulisHSV-1, HSV-2 (50)
Geranium sanguitneumHSV-1, HSV-2 (3.6-6)
PropolisHSV-1, VZV, HSV-2
Alkaloids
CepharanthineStephania cepharanthaHSV
FK-3000Stephania cepharanthaHSV-1 (7.8)
HarmineOphiorrhiza nicobaricaHSV-2 (300)
Bis-benzylisoquinoline
ProtoberberineStephania cepharantha HayataHSV-1 (18)
N-methylcrotsparineHSV-1, HSV-2 (7.8-9.9) (90, 71, 81)
Phenolics
Caffeic acidPlantago majorHSV-1 (15.3), VZV
P. majorHSV-2 (87.3)
ChlorogenicacidAloe barbadensitsHSV-1 (47.6)
HSV-2 (86.5)
Procyanidin A1Vaccinium vittits-itdacaHSV-2
Procyanidin C1Crataegus sitnaitcaHSV-1
Prodelphinidine-o-gallateMyrica rubraHSV-2 (5.3)
RosmarinicacidPlantago majorVZV
XanthohumolHumulus lupulusHSV
PolyphenolsGeranium sanguitneum LHSV-1, HSV-2 (3.6-6.2)
Cochinolide B, tremulacinHomalium cochinchinensisHSV-1.HSV-2
AsiaticosideCentella asitatitcaHSV
MangiferinMangifera tnditcaHSV-1, HSV-2
Rutin, rutin sulphateHSV-1 (3-8.8)
PhenolicsRheum officinaleHSV-1
Paeonia suffrutitcosaHSV-1
Melia toosendanHSV-1
Flavonoitds
CatechinCitrus aurantium, Vittits vitnitferaHSV-1
HesperidinOrange, grapeHSV
ResveratrolHSV
OxyresveratrolMillettia erythrocalyxHSV
QuercetinCaesalpinia pulcherritmaHSV-1 (24.3), (20)
Phloroglucinol methyl gallateMallotus japonicusHSV
ApigeninOcimum basillicumHSV-1
EpiafzelechinCassia javanicaHSV-2
Terpenes/sterols
Betulinic acidOcitmum basilicum, RhusjavanitcaHSV (2.6)
IsoborneolMelaleuca alternifoliaHSV-1, 2(0.06)
LupenoneEuphorbia segetalitsHSV-1, HSV-2
Moronic acidMyrceugenia euosma, R. javanitcaHSV (3.9), HSV-2
Glycyrrhetinic acidGlycyrrhitzitn glabraHSV-1
PulegoneMinthostachys verticil lataHSV-1 (10)
Putranjivain AEuphorbia jolkiniHSV-2, (6.3 μM)
Ursolic acidHSV-1
Sclerocarpic acid (sesquiterpene)Glyptopetalum sderocarpumHSV-1, HSV-2
Scopadulcicacid B (diterpenoid)Scoparia duicits L.HSV-1 (16.7)
MorinMadura cochitnchitnensisHSV-2 (38.5-53)
QuassinoidsEBV
28-deacetylsendanin (Limonoid)Melia azedarachHSV-1(1.46)
MeliacineMelia azedarachHSV-1
AsiaticosideCentella asitatitca L.HSV-1, HSV-2
MangiferinMangifera tnditca L.HSV-1, HSV-2
Cochinolide B, tremulacinHomalitum cochitnchitnensisHSV-1 , HSV-2
Essential oilMinthostachys verticillataHSV
Artemisia arborescenHSV-2
Black seed oilNigella satitvaMCMV
N-N-B5Nelumbo nucitferaHSV-1, HSV-2 (50-62)
ThiazolylsulphonamideHSV
n-docosanolHSV-1
OryzacystatinOryzae satitvaHSV-1
Saponins
8-Acetylharpagide, scorodiosideBupleurum nitgidumHSV-1 (500)
SaikosaponinScrophularita scorodonitaVSV
Saponin glycosides (spirostane, tomatidane)Solanum spp.HSV-1
Tannin
CasuarininTerminalia arjunaHSV-2(1.5 μM)
EugeniinGeum japonitcumHSV-1, HSV-2, EBV
Syzygitum aromatitcumHSV, VZV
Samaragenin BLimonitum sitnensitHSV-1
EllagitanninsPhyllanthus myrtitfolius, P. urinariaEBV
Euglobal-G1,G2,G3Eucalyptus granditsEBV
n-docosanolHSV-1
Lignans
LignanRhus javanitcaHSV-2
YateinChamaecyparits obtusaHSV-1
Carbohydrate
PolysaccharideSelerotium glucanitcumHSV-1
Anionic polysaccharidePrunella vulgarisHSV-I(100), HSV-2(10)
Polysaccharide lignan complexPrunella vulgarisHSV-1, HSV-2 (20—100)
Sulphated galactansBostrychia montagneitHSV
GalactofucanUndaria pitnnatitdaHSV-1, HSV-2
Proteins and peptides
Mannose-specific lectinsListera ovataCMV (0.08)
GlcNAc) n-specific lectinUrtica dioicaCMV (0.3—9)
PeptideSorghum bitcolorHSV-1

HSV = herpes simplex virus; VZV = varicella zoster virus; CMV = cytomegalovirus; MCMV = murinecytomegalovirus; EBV = Epstein-Barr virus.