In vivo antiplasmodial activity of 11(13)-dehydroivaxillin from Carpesium ceruum

The whole plants of Carpesium genus are used in traditional medicine as anti-pyretic, analgesic and vermifugic, including a topical application for sores and inflammation. A previous study on Carpesium genus suggested that the antiplasmodial activity against Plasmodium falciparum was due to the existence of 11(13)- dehydroivaxillin (DDV) from EtOAc extracts of C. ceruum (Compositae). Here, the antimalarial activity of DDV was evaluated against Plasmodium berghei in mice. The LD(50) of the compound was determined as 51.2 mg/kg, while doses of 124 mg/kg and above were found to be lethal to mice. DDV (2, 5, 10 mg/kg/day) exhibited a significant blood schizontocidal activity in 4-day early infection, repository evaluation and in an established infection with a significant mean survival time comparable to that of the standard drug, chloroquine, 5 mg/kg/day. DDV possesses a promising antiplasmodial activity, which can be exploited in malaria therapy.     

In vitro and in vivo antimalarial evaluation of semi-synthetic derivatives of gomphostenin

A novel series of semi-synthetic gomphostenin derivatives (1–9) were prepared utilizing C-14 hydroxyl group for the first time and studied for their antimalarial properties. In vitro antiplasmodial activity was evaluated against both the chloroquine sensitive and resistant strains of Plasmodium falciparum. Most of the compounds exhibited superior or comparable antiplasmodial activity compared to parent compound, that is, gomphostenin (GN). Based upon in vitro antiplasmodial activity, compounds with IC₅₀ values less than 10 μM were selected for in vivo antiplasmodial evaluation against Plasmodium berghei infection in mice model. GN derivatives 3 and 5 were found to have curative activity with moderate chemosuppression of 65% and 69%, respectively, at the dose level of 150 mg/kg/day.     

Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships

Piperazine and pyrrolidine derivatives were synthesised and evaluated for their capacity to inhibit the growth of Plasmodium falciparum chloroquine-resistant (FCR-3) strain in culture. The combined presence of a hydroxyl group, a propane chain and a fluor were shown to be crucial for the antiplasmodial activity. Five compounds of the aryl-alcohol series inhibited 50% of parasite growth at doses ?10 μM. The most active compound 1-(4-fluoronaphthyl)-3-[4-(4-nitro-2-trifluoromethylphenyl)piperazin-1-yl] propan-1-ol was almost 20–40 times more active on P. falciparum (IC₅₀: 0.5 μM) than on tumorogenic and non-tumorogenic cells. In vivo it has a very weak effect; inhibiting 35% of parasite growth only, at 10 mg/kg/day against Plasmodium berghei infected mice without any impact on survival time. In silico molecular docking study and molecular electrostatic potential calculation revealed that this compound bound to the active site of Plasmodium plasmepsin II enzyme.     

Antiplasmodial and cytotoxicity activities of some selected plants used by the Maasai community, Kenya

Malaria has continued to be a major global public health problem and a health concern in most of African countries. An estimated 350–500 million cases of malaria each year result in about one million deaths, mainly children under five. The rate of malaria infection is increasing rapidly partly due to drug resistance by the Plasmodium falciparum. The cost of the current drugs is prohibitive to the poor. There is therefore urgent need to identify new antimalarial agents that are effective, safe and affordable. In our continuous search for these new antimalarial compounds, extracts from five medicinal plants from the Maasai community in Kenya were tested against P. falciparum (D6; chloroquine sensitive and W2; chloroquine resistant strains). Of the tested total plant extracts, 5 crude extracts showed good antiplasmodial activity against D6 strain of P. falciparum with IC₅₀ values lower or equal to 14.3 μg/ml, 2 were moderately active with IC₅₀ values in between 26.6 and < 50 μg/ml. The petroleum ether extracts of the aerial parts and roots of Fuerstia africana demonstrated high antiplasmodial activity against the chloroquine sensitive antiplasmodial strain D6 (IC₅₀ 1.5 and 4.6 μg/ml, respectively with a selectivity index of 44 against vero cells). Manilkara discolor also exhibited promising antiplasmodial activity especially against D6 (IC₅₀ 11.5 and 26.6 μg/ml). In addition, ethyl acetate extract of the roots of Pentas lanceolata and the aerial parts of Sericocomopsis hildebrandtii demonstrated moderate antiplasmodial activity against D6 and W2 (IC₅₀ 14.3 and 16.51 μg/ml) respectively. F. africana therefore has high potential and can be pursued for the development of an antimalarial drug.     

Antimalarial activity of endoperoxide compound 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol

Plasmodium falciparum, the major causative parasite for the disease, has acquired resistance to most of the antimalarial drugs used today, presenting an immediate need for new antimalarial drugs. Here, we report the in vitro and in vivo antimalarial activities of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against P. falciparum and Plasmodium berghei parasites. The N-251 showed high antimalarial potencies both in the in vitro and the in vivo tests (EC₅₀ 2.3 × 10⁻⁸ M; ED₅₀ 15 mg/kg (per oral)). The potencies were similar to that of artemisinin in vitro and greater than artemisinin's activity in vivo (p.o.). In addition, N-251 has little toxicity: a single oral administration at 2000 mg/kg to a rat gave no health problems to it. Administration of N-251 to mice bearing 1% of parasitemia (per oral 68 mg/kg, 3 times a day for 3 consecutive days) resulted in a dramatic decrease in the parasitemia: all the 5 mice given N-251 were cured without any recurrence, with no diarrhea or weight loss occurring in the 60 days of experiment. N-251 deserves more extensive clinical evaluation, desirably including future trials in the human.     

Antiplasmodial effects of the aqueous extract of Phyllantus amarus Schumach and Thonn against Plasmodium berghei in Swiss albino mice.

Phyllantus amarus Schumach and Thonn is a medicinal plant used commonly for the treatment of malaria-related symptoms by the general public in southeastern Nigeria. The present study determines the possible antiplasmodial effects of the aqueous extract of the leaves and stem of the plant against Plasmodium berghei infection using Swiss albino mice as models. The blood schizonticidal activity of the aqueous extract in early infection and in established Plasmodium berghei infection was assessed and compared to the activities of chloroquine and sulfadoxine/pyrimethamine. The repository activity of the extract was also assessed and compared to the activity of pyrimethamine. The LD50 of the aqueous extract of the leaves and stem of the plant was also determined using albino Wistar rats. The results show that the LD50 of the aqueous extract of Phyllantus amarus Schumach and Thonn was 650 mg/kg. In early infection, the extract at doses of 108.33 mg/kg, 165 mg/kg and 325 mg/kg was found to cause a significant dose-dependent suppression of P berghei parasites [P < P0.05] sulfadoxine/pyrimethamine caused a similar significant suppression of P berghei parasites [P < 0.05] while chloroquine at a dose of 5 mg/kg did not cause a significant effect on P berghei parasites. Similarly, the extract was found at all doses to cause a statistically significant [P < 0.05] suppression of P berghei parasites via a repository action. This effect was comparable to the effects of pyrimethamine a standard repository agent. In established infection, the extract at all doses administered, was found to significantly suppress P berghei parasites at 24 and 72-hour periods [P < 0.05]. Comparatively, sulfadoxine/pyrimethamine caused a similar statistical [P < 0.05] suppression of the parasites of P. berghei. However, the effects of sulfadoxine/pyrimethamine were more sustained over the 72-hour period. The present study therefore validates the local use of the extracts of Phyllantus amarus Schumach and Thonn as an antimalarial agent. Further studies are however recommended to identify and possibly characterize the potential antiplasmodial agents in the aqueous extract of the plant.     

Hepatoprotective effect of bis(4‐methylbenzoyl) diselenide against CCl4‐induced oxidative damage in mice

From a pharmacological point of view, organoseleniums are compounds with important and interesting antioxidant and biological activities. The aim of this study was to evaluate the hepatoprotective effect of bis(4‐methylbenzoyl) diselenide (BMD) against carbon tetrachloride (CCl₄)–induced oxidative damage in mice. The animals received BMD (25 mg/kg p.o., for 3 days), and after 1 day, CCl₄ (1 mg/kg body weight) was administered by intraperitoneal route. One day after the CCl₄ exposure, the animals were euthanized for biochemical and histological analysis. Treatment with BMD (25 mg/kg p.o.) protected against aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma‐glutamyl transferase and lactate dehydrogenase activity increases induced by CCl₄ plasma exposure. Treatment with BMD (25 mg/kg) protected against increases in thiobarbituric reactive species and decreasing non‐protein thiols and ascorbic acid levels in liver of mice. Catalase and superoxide dismutase activity inhibition in the liver caused by CCl₄ were protected by treatment with BMD (25 mg/kg). Glutathione S‐transferase activity was inhibited by CCl₄ and remained unaltered even after treatment with BMD. Sections of liver from CCl₄‐exposed mice presented an intense infiltration of inflammatory cells and loss of the cellular architecture. BMD (25 mg/kg) attenuated CCl₄‐induced hepatic histological alterations. The results demonstrated the hepatoprotective effects of BMD in the mouse liver, possibly by modulating the antioxidant status. Copyright © 2012 John Wiley & Sons, Ltd.     

Alpha-glucosidase inhibitory and antiplasmodial properties of terpenoids from the leaves of Buddleja saligna Willd

In our continuing search for biologically active natural product(s) of plant origin, Buddleja saligna, a South African medicinal plant, was screened in line with its traditional use for antidiabetic (yeast alpha glucosidase inhibitory) and antiplasmodial (against a chloroquine sensitive strain of Plasmodium falciparum (NF54)) activities. The hexane fraction showed the most promising activity with regards to its antidiabetic (IC₅₀?=?260?±?0.112?µg/ml) and antiplasmodial (IC₅₀?=?8.5?±?1.6?µg/ml) activities. Using activity guided fractionation three known terpenoids (betulonic acid, betulone and spinasterol) were isolated from this species for the first time. The compounds displayed varying levels of biological activities (antidiabetic: 27.31?µg/ml?≥?IC₅₀?≥?5.6?µg/ml; antiplasmodial: 14?µg/ml?≥?IC₅₀?≥?2?µg/ml) with very minimal toxicity.     

Activity-guided isolation of antiplasmodial dihydrochalcones and flavanones from Piper hostmannianum var. berbicense

The bioassay-guided purification of an n-hexane extract from the leaves of Piper hostmannianum var. berbicense led to the isolation of four monoterpene or prenyl-substituted dihydrochalcones (1a, 1b, 2, 3) as well as the known compounds 2',6'-dihydroxy-4'-methoxydihydrochalcone (4), linderatone (5), strobopinin (6), adunctin E (7) and (-)-methyllinderatin (8). Their structures were established on the basis of NMR and X-ray analysis. (-)-Methyllinderatin, linderatone and 2',6'-dihydroxy-4'-methoxydihydrochalcone exhibited the most potent antiplasmodial activity with IC50 values of 5.64, 10.33 and 12.69 microM, respectively against both chloroquine-sensitive and resistant strains of Plasmodium falciparum (F32,FcB1). The activity of (-)-methyllinderatin was confirmed in vivo against Plasmodium vinckei petteri in mice (80% of reduction of parasitemia) at a dose of 20 mg/kg/day.     

Antiplasmodial activity of Morinda lucida Benth. Leaf and bark extracts against Plasmodium berghei infected mice

Ethnopharmacology relevanceMorinda lucida is an ethnopharmacologically important plant that has traditionally been used to treat malaria in the Southwest of Nigeria. The aim of this study is to look into the antiplasmodial properties of different solvent extracts of Morinda lucida bark and leaves.Materials and methodsThe antiplasmodial model, (or curative assay), was tested against Plasmodium berghei NK65, a chloroquine-sensitive Plasmodium berghei strain. In experimental mice, parasitaemia, percentage inhibition, weight changes, and packed cell volume were measured and compared to chloroquine (10 mg kg^?1). Standard phytochemical procedures were used to evaluate the extracts' chemo-profile.Results and DiscussionPhytochemical analysis of the extracts revealed the presence of tannins, alkaloids, steroids, saponins, phenols, and alkaloids, among other metabolites. The highest quantities of total phenolic, total tannins, and total flavonoid content were found in 50% ethanolic extracts. There was significant decrease in the body weight of the mice after inoculation, however, after administration of crude extracts, an increase in weight was observed. A negative variation (-3.00 g) was observed in group without treatment. The ethanolic crude extracts (200 and 400 mg/kg) significantly increased the packed cell volume compared to other extracts. CQ treated experimental mice showed 100% inhibition with activity greater than extracts treated groups. The lowest inhibitory effect was observed in 200 mg/kg ethanolic bark extract treated group with activity of 72.16%. The antiplasmodial activities exhibited by these extracts could be linked to the chemical constituents investigated.ConclusionThe findings of this study suggest the use of M. lucida leaves and bark as a medicinal agent for malaria treatment and as a potential source of effective antimalarial templates. Further research is needed to determine the safety and toxicological profile of these extracts in vivo.     

Azithromycin: antimalarial profile against blood- and sporozoite-induced infections in mice and monkeys

The spectrum of antimalarial activity of the new macrolide antibiotic azithromycin was evaluated against blood- and sporozoite-induced infections with a chloroquine-resistant strain of Plasmodium yoelii nigeriensis (N-67) in Swiss mice and with simian parasite Plasmodium cynomolgi B in rhesus monkeys. Against experimental rodent malaria, a 70 mg/kg/day dose showed curative blood-schizontocidal activity in a four-dose regimen administered orally from day 0 to day 3 or from day 2 to day 5 to mice harboring established infection. The curative response was also obtained with a 40 mg/kg/day dose administered in an extended seven-dose (days 0-6) regimen. Azithromycin was also effective in the causal prophylactic test, since a 50 mg/kg dose from day -1 to day +2 protected mice against P. y. nigeriensis (N-67) sporozoite challenge. In comparison, erythromycin did not show either of the above activities up to a 405 mg/kg/day dose in identical regimens. Comparison of the ED(90) values showed that azithromycin was 31-fold more effective than erythromycin as a blood schizontocide. In the simian model, trophozoite-induced infections of P. cynomolgi B were cured with 25 mg/kg/day azithromycin administered for 7 days. In the causal prophylactic test, the prepatent period was significantly extended in monkeys challenged with P. cynomolgi B sporozoites, presumably because of the growth inhibition of preerythrocytic schizonts in hepatocytes. Azithromycin did not exhibit any hypnozoitocidal (dormant exoerythrocytic stages) activity at 25 mg/kg/day in a seven-dose regimen.     

The antimalarial activity of Ru–chloroquine complexes against resistant Plasmodium falciparum is related to lipophilicity, basicity, and heme aggregation inhibition ability near water/n-octanol interfaces

We have measured water/n-octanol partition coefficients, pK _a values, heme binding constants, and heme aggregation inhibition activity of a series of ruthenium–π-arene–chloroquine (CQ) complexes recently reported to be active against CQ-resistant strains of Plasmodium falciparum. Measurements of heme aggregation inhibition activity of the metal complexes near water/n-octanol interfaces qualitatively predict their superior antiplasmodial action against resistant parasites, in relation to CQ; we conclude that this modified method may be a better predictor of antimalarial potency than standard tests in aqueous acidic buffer. Some interesting tendencies emerge from our data, indicating that the antiplasmodial activity is related to a balance of effects associated with the lipophilicity, basicity, and structural details of the compounds studied. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Dialkylaminoalkyl derivatives of bicyclic compounds with antiplasmodial activity

Dialkylaminoalkyl derivatives of 2-azabicyclo[3.2.2]nonanes and of bicyclo[2.2.2]octanes were prepared and their activities determined in vitro against the multiresistant K₁ strain of Plasmodium falciparum. Several of the new compounds exhibited very promising antiplasmodial activity and selectivity. The results were compared to those of formerly synthesized analogues and of drugs in use. Structure–activity relationships were detected. Some of the more potent compounds were tested in vivo against Plasmodium berghei showing weak to moderate activity. A single compound was able to increase the mean survival days of infected mice.     

Experimental treatment of Neospora caninum-infected mice with the arylimidamide DB750 and the thiazolide nitazoxanide

The cationic arylimidamide DB750 and the thiazolide nitazoxanide had been shown earlier to be effective against Neospora caninum tachyzoites in vitro with an IC₅₀ of 160 nM and 4.23 μM, respectively. In this study, we have investigated the effects of DB750 and nitazoxanide treatments of experimentally infected Balb/c mice, by applying the drugs either through the oral or the intraperitoneal route. In experiment 1, administration of DB750 (2 mg/kg/day) and nitazoxanide (150 mg/kg/day) started already 3 days prior to experimental infection of mice with 2 × 10⁶ tachyzoites. Following infection, the drugs were further administrated daily for a period of 2 weeks, either orally or intraperitoneally. Intraperitoneal injection of DB750 was well tolerated by the mice, but treatment with nitazoxanide resulted in death of all mice within 3 days. Upon intraperitoneal application of DB750, the cerebral parasite load was significantly reduced compared to all other groups, while oral application of DB750 and nitazoxanide were not as effective, and resulted in significant weight loss. In experiment 2, mice were infected with 2 × 10⁶ tachyzoites and at 2 weeks post-infection, DB750 (2 mg/kg/day) was applied by intraperitoneal injections for 14 days. In the DB750-treated group, only 2 out of 12 mice succumbed to infection, compared to 7 out of 12 mice in the placebo-group. DB750 treatment also resulted in significantly reduced cerebral parasite burden, and reduced numbers of viable tachyzoites. Our data suggest that DB750 exerted its activity also after crossing the blood–brain barrier, and that this class of compounds could be promising for the control of N. caninum-associated disease.     

Anti‐infectious activity of synbiotics in a novel mouse model of methicillin‐resistant Staphylococcus aureus infection

The anti‐infectious activity of synbiotics against methicillin‐resistant Staphylococcus aureus (MRSA) infection was evaluated using a novel lethal mouse model. Groups of 12 mice treated with multiple antibiotics were infected orally with a clinical isolate of MRSA at an inoculum of 10⁸ CFU on day 7 after starting the antibiotics. A dose of 400 mg/kg 5‐fluorouracil (5‐FU) was injected intraperitoneally on day 7 after the infection. A dose of 10⁸ CFU Bifidobacterium breve strain Yakult and 10 mg of galactooligosaccharides (GOS) were given orally to mice daily with the antibiotic treatment until day 28. The intestinal population levels of MRSA in the mice on multiple antibiotics were maintained stably at 10⁸ CFU/g of intestinal contents after oral MRSA infection and the subsequent 5‐FU treatment killed all the mice in the group within 14 days. B. breve administration saved most of the mice, but the synbiotic treatment saved all of the mice from lethal MRSA infection. The synbiotic treatment was effective for the treatment of intestinal infection caused by four MRSA strains with different toxin productions. There was a large difference among the six Bifidobacteria strains that were naturally resistant to the antibacterial drugs used. B. breve in combination with GOS is demonstrated to have valuable preventive and curative effects against even fatal MRSA infections.     

Evaluation of substituted phenalenone analogues as antiplasmodial agents

A set of derivatives encompassing structural modifications on the privileged phenalenone scaffold were assessed for their antiplasmodial activities against a strain of chloroquine sensitive Plasmodium falciparum F32. Two compounds exhibited considerable effects against the malaria parasite (IC₅₀ ? 1 μg/mL), one of which maintained the same level of activity in a chloroquine-resistant strain. This is the first record of antiplasmodial activity on this type of scaffold, providing a new structural motif as a new lead for antimalarial activity.     

Antiprotozoal activity of dicationic 3,5-diphenylisoxazoles,their prodrugs and aza-analogues

Fifty novel prodrugs and aza-analogues of 3,5-bis(4-amidinophenyl)isoxazole and its derivatives were prepared. Eighteen of the 24 aza-analogues exhibited IC₅₀ values below 25 nM against Trypanosoma brucei rhodesiense or Plasmodium falciparum. Six compounds had antitrypanosomal IC₅₀ values below 10 nM. Twelve analogues showed similar antiplasmodial activities, including three with sub-nanomolar potencies. Forty-four diamidines (including 16 aza-analogues) and the 26 prodrugs were evaluated for efficacy in mice infected with T. b. rhodesiense STIB900. Six diamidines cured 4/4 mice at daily 5 mg/kg intraperitoneal doses for 4 days, giving results far superior to pentamidine and furamidine. One prodrug attained 3/4 cures at daily 25 mg/kg oral doses for 4 days.     

Protection of mice from malaria after co-administration of recombinant mouse granulocyte-macrophage colony- stimulating factor and methionine-enkephalin

The protective effect of co-administration of recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and synthetic peptide met-enkephalin (M-ENK) against blood-induced Plasmodium berghei infection in Swiss mice was investigated. Mice co-administered with rmGM-CSF (10.0 mug/kg) and M-ENK (2.0 mg/kg) x 3/day, i.p., beginning on day -1 and continuing through day +4 after the initiation of infection, showed significant suppression (p < 0.05) (sometimes even complete elimination) of parasitaemia compared to vehicle-treated controls. However, when administered separately, neither of these agents induced any detectable protective effect. Surprisingly, mice similarly co-administered with rmGM-CSF (10.0 mug/kg) and higher doses of M-ENK (10.0 mg/kg), showed no protection. Polyclonal neutralizing (100%) antibody to rmGM-CSF abrogated the combined protective effect of these agents. Additionally, naloxone (10.0 mg/kg/day x 6, i.p.), a non-selective, opioid receptor antagonist, also blocked the combined protection. Mice that survived the challenge showed a significant increase (p < 0.05) in total circulating leukocytes counts, and the pool-size and the phagocytic activity of both the peritoneal and splenic macrophages, ex vivo. Silica (3.0 mg/mouse, i.v.) abrogated the combined protective effect of rmGM-CSF and M-ENK. These results indicate that co-administration of rmGM-CSF and dose dependent quantities of M-ENK in P. berghei-infected mice can protect against malaria, apparently through macrophage-mediated mechanisms.     

Antiplasmodial and Cytotoxic Activities of Extract and Compounds from Ozoroa obovata (Oliv.) R. & A. Fern. var. obovata

Ozoroa obovata (Oliv.) R. & A. Fern. var. obovata found in KwaZulu-Natal in South Africa was investigated for phytochemical constituents, and for antiplasmodial and cytotoxic effects. The plant leaves were collected from the University of KwaZulu-Natal (UKZN) arboretum on the Pietermaritzburg Campus, in March 2019. The inhibitory activity against 3D7 Plasmodium falciparum was determined using the parasite lactate dehydrogenase (pLDH) assay and cytotoxicity against HeLa cells was evaluated using the resazurin assay. The bioactive compounds were isolated by chromatographic purification and their structures were established with spectroscopic and spectrometric techniques. The plant leaf extract displayed significant antiplasmodial activity at 50 μg/mL and was also cytotoxic against HeLa cells. Chromatographic purification of the extract led to the isolation of two biflavonoids, four flavonoid glycosides, a steroid glycoside, and a megastigmene derivative. The compounds displayed antiplasmodial and antiproliferative activities at 50 μg/mL but the activity was substantially reduced at 10 μg/mL. The activities and compounds are being reported in O. obovata for the first time.     

Antiviral activity of recombinant cyanovirin-N against HSV-1

In this study, a standard strain of HSV-1 (strain SM₄₄) was used to investigate the antiviral activity of the recombinant Cyanovirin-N (CV-N) against Herpes simplex virus type 1 (HSV-1) in vitro and in vivo. Cytopathic effect (CPE) and MTT assays were used to evaluate the effect of CV-N on HSV-1 in Vero cells. The number of copies of HSV-DNA was detected by real-time fluorescence quantitative PCR (FQ-PCR). The results showed that CV-N had a low cytotoxicity on Vero cells with a CC₅₀ of 359.03±0.56 μg/mL, and that it could not directly inactivate HSV-1 infectivity. CV-N not only reduced the CPE of HSV-1 when added before or after viral infection, with a 50% inhibitory concentration (IC₅₀) with 2.26 and 30.16μg/mL respectively, but it also decreased the copies of HSV-1 DNA in infected host cells. The encephalitis model for HSV-1 infection was conducted in Kunming mice, and treated with three dosages of CV-N (0.5, 5 &; 10 mg/kg) which was administered intraperitoneally at 2h, 3d, 5d, 7d post infection. The duration for the appearance of symptoms of encephalitis and the survival days were recorded and brain tissue samples were obtained for pathological examination (HE staining). Compared with the untreated control group, in the 5mg/kg CV-N and 10mg/kg CV-N treated groups, the mice suffered light symptoms and the number of survival days were more than 9d and 14d respectively. HE staining also showed that in 5mg/kg CV-N and 10mg/kg CV-N treated groups, the brain cells did not show visible changes, except for a slight inflammation. Our results demonstrated that CV-N has pronounced antiviral activity against HSV-1 both in vitro and in vivo, and it would be a promising new candidate for anti-HSV therapeutics.