Inhibitory effects of Korean medicinal plants and camelliatannin H from Camellia japonica on human immunodeficiency virus type 1 protease

To identify substances with anti-human immunodeficiency virus (HIV) activity in traditional medicines, 101 extracts of Korean medicinal plants were screened for their inhibitory effects on HIV type 1 protease (PR). The enzyme activity was determined by HPLC. Of the extracts tested, strong inhibitory effects were observed in the acetone extracts of the pericarp and leaves of Camellia japonica, the water extract of the leaves of Sageretia theezans and the methanol extract of the aerial part of Sophora flavescens. Camelliatannin H from the pericarp of C. japonica, showed a potent inhibitory activity on HIV-1 PR with IC(50) of 0.9 microM.     

Screening of Traditional Medicines for their Inhibitory Activity Against HIV-1 Protease

Aqueous extracts of 75 different traditional medicines, currently used for the treatment of various human diseases in China, Japan and Indonesia, were screened for possible inhibitory activity against HIV-1 protease using fluorogenic assay. Forty extracts exhibited inhibitory activity at a concentration of 250 μg/mL, and 18 of them inhibited HIV-1 protease activity by more than 70%. Among the extracts examined, Belamcanda chinensis, Magnolia fargesii, Paeonia suffruticosa, Phellodendron amurense and Terminalia chebula were also effective at a concentration of 25 μg/mL in the fluorogenic assay.     

6种藏族药提取物体外抗HIV-1活性的初步探讨

目的:对斑花黄堇、木藤蓼、野棉花、黄花铁线莲、黑心虎耳草和短尾铁线莲6种藏药提取物的体外抗艾滋病病毒Ⅰ型(HIV-1)病毒活性的评价及其作用机制的初步研究。方法:采用细胞计数试剂盒(CCK-8)法细胞毒性实验和HIV-1假病毒单周期感染实验检测提取物的体外抗病毒活性和细胞毒性;利用表面等离子共振(surface plasmon resonance,SPR)技术、蛋白酶、整合酶和逆转录酶体外活性抑制实验初步探讨药物的作用靶点。结果:在这6种藏药提取物中,木藤蓼、野棉花、黑心虎耳草提取物具有较好的体外抗HIV-1病毒活性,半数抑制浓度(half maximal inhibitory concentration,IC50)分别为(6.47±0.78),(11.97±1.09),(11.7±0.79)mg·L-1,且细胞毒性较小,三者均具有较好的体外抑制整合酶活性。结论:木藤蓼、野棉花、黑心虎耳草提取物具有较好的抗HIV-1病毒的作用,其作用机制与整合酶的抑制作用有关。     

Old plants newly discovered: Cassia sieberiana D.C. and Cassia abbreviata Oliv. Oliv. root extracts inhibit in vitro HIV-1c replication in peripheral blood mononuclear cells (PBMCs) by different modes of action

Ethnopharmacological relevance

Despite advances in anti-retroviral therapy which has transformed HIV/AIDS from a fatal to a manageable chronic disease, increasing viral drug resistance, side effects and uneven access to anti-retroviral drugs remain considerable therapeutic challenges. Partly as a consequence of these shortcomings and partly based on the fact that HIV/AIDS gives rise to opportunistic infections whose symptoms have been managed in Africa in an HIV/AIDS-independent context by traditional healers for centuries, many HIV/AIDS patients use herbal medicines. The aim of this study was to screen selected medicinal plants from Botswana, used by traditional healers to treat/manage HIV/AIDS, for inhibitory activities on HIV replication.

Materials and methods

Based on an ethnomedical survey, ethanolic tannin-containing and tannin-free extracts from 10 medicinal plants were tested for inhibitory properties against a clone of HIV-1c (MJ₄) measuring cytopathic effect protection and levels of viral p24 antigen in infected PBMCs.

Results

Cassia sieberiana D.C., Cassia abbreviata Oliv. Oliv. and Plumbago zeylanica L. extracts showed significant inhibition of HIV-1c (MJ₄) replication. The inhibitory activity of the Plumbago zeylanica extract could be attributed to its tannin content. Anti-HIV activity of Cassia sieberiana root and bark extracts, and Cassia abbreviata root extracts occurred in a concentration-dependent manner with an effective concentration (EC₅₀) of 65.1 μg/ml, 85.3 μg/ml and 102.8 μg/ml, respectively. Experiments to elucidate possible mechanism(s) of action revealed that Cassia sieberiana root and bark extracts blocked HIV replication at its binding- (EC₅₀ = 70.2 μg/ml and 90.8 μg/ml, respectively) and entry stage (EC₅₀ = 88.9 μg/ml and 100.5 μg/ml, respectively) while Cassia abbreviata extracts did not.

Conclusions

We report here for the first time a direct inhibitory effect on HIV-1c replication of extracts from two extremely popular medicinal plants, Cassia sieberiana and Cassia abbreviata. Considering the traditional uses of both Cassia species, our findings strongly suggest pilot clinical observational studies involving traditional healers to further evaluate the therapeutic potential of the Cassia extracts.     

Screening of Indonesian plant extracts for anti-human immunodeficiency virus—type 1 (HIV-1) activity

Of 30 Indonesian plant extracts tested for their human immunodeficiency virus type-1 (HIV-1) inhibitory activities, six were shown to be effective by assays using HIV-1-infected MT-4 cells: a methanol extract of mahoni (bark of Swietenia mahagoni) and water extracts of benalu teh (stems and branches of Loranthus parasiticus), kiules (fruit of Helicteres isora), supratul (fruits of Sindora sumatrana), sambiloto (leaves of Andrographis paniculata) and temu ireng (rhizoma of Curcuma aeruginosa). Their ED₅₀ values ranged from 4.2 to 175 μg/mL. The samples also suppressed the formation of syncytia in co-cultures of MOLT-4 and MOLT-4/HIV-1 cells. The most potent inhibitor was a methanol extract of mahoni, which also showed a significant inhibition of HIV-1 protease.     

Inhibitory effects of Sudanese plant extracts on HIV-1 replication and HIV-1 protease

Forty-eight methanol and aqueous extracts from Sudanese plants were screened for their inhibitory activity on viral replication. Nineteen extracts showed inhibitory effects on HIV-induced cytopathic effects (CPE) on MT-4 cells. The extracts were further screened against HIV-1 protease (PR) using an HPLC assay method. Of the tested extracts, the methanol extracts of Acacia nilotica (bark and pods), Euphorbia granulata (leaves), Maytenus senegalensis (stem-bark) and aqueous extracts of A. nilotica (pods) and M. senegalensis (stem-bark) showed considerable inhibitory effects against HIV-1 PR. Inhibitory principles were isolated from M. senegalensis and their activities were also discussed.     

Screening of New Zealand Plant Extracts for Inhibitory Activity Against HIV-1 Protease

231 Ethanol/aqueous extracts from New Zealand plants were screened for inhibitory activity against HIV-1 protease using fluorogenic and HPLC assays. Among the examined extracts, Pseudotsuga menziesii , Elaeocarpus hookerianus , Pernettya macrostigma and Cassinia leptophylla showed significant inhibition at a concentration of 50 μg/mL in the HPLC confirmation assay. The IC₅₀ values of these extracts to HIV-1 protease on its synthetic peptide substrate were 9.63, 9.74, 27.62 and 60.73 μg/mL, respectively. The derivatives of dihydroquercetin and [5′5′]-bisdihydroquercetin from Pseudotsuga menziesii could be the causative compounds for the inhibition.     

A human immunodeficiency virus protease inhibitory substance from Swietenia mahagoni

For the purpose of finding anti-HIV agents from natural sources, various plant extracts were screened for their inhibitory activity against HIV-protease, an enzyme essential for viral proliferation. By bioassay-directed fractionation of the methanol extract of Swietenia mahagoni (bark) which had shown inhibitory activity against this enzyme, we isolated and identified chlorogenic acid methyl ester as a inhibitory substance, its 50% inhibitory concentration being less than 40 μg/ml. © 1997 John Wiley & Sons, Ltd.     

HIV-1 protease and HIV-1 integrase inhibitory substances from Eclipta prostrata

The bioassay-guided fractionation for anti-HIV-1 integrase activity led to the isolation of six compounds from the whole plant extract of Eclipta prostrata extract. They were identified as 5-hydroxymethyl-(2,2':5',2')-terthienyl tiglate (1), 5-hydroxymethyl-(2,2':5',2')-terthienyl agelate (2), 5-hydroxymethyl-(2,2':5',2')-terthienyl acetate (3), ecliptal (4), orobol (5) and wedelolactone (6). Of these, compound 6 showed the highest activity against HIV-1 integrase (IN) with an IC50 value of 4.0+/-0.2 microm, followed by compound 5 (IC50=8.1+/-0.5 microm), whereas the four terthiophene compounds (1-4) were inactive (IC50>100 microm). Regarding HIV-1 protease (PR) inhibitory activity, compound 1 exhibited appreciable activity against HIV-1 PR with an IC50 of 58.3+/-0.8 microm, followed by compound 4 (IC50=83.3+/-1.6 microm) and compound 3 (IC50=93.7+/-0.8 microm), while compounds 2, 5 and 6 were inactive against HIV-1 PR (IC50>100 microm). This is the first report of anti-HIV-1 IN activities for wedelolactone (6), a coumarin derivative, and orobol (5), an isoflavone derivative. This study supports the use of E. prostrata in AIDS patients, which is in accord with its traditional use by Thai traditional doctors for curing blood related diseases.     

In vitro Activity of Extracts from Polyporaceae against Human Immunodeficiency Virus Type 1

Aqueous extracts of Fomitella supina, Phellinus rhabarbarinus, Trichaptum perrottettii, and Trametes cubensis (Polyporaceae) from the Amazonian rain forest of Venezuela exhibited differential cytotoxicity and inhibitory activity against the human immunodeficiency virus type 1 (HIV-1). These extracts inactivated extracellular virions and suppressed HIV-1 replication by blocking HIV-1-induced cell–cell fusion in an in vitro culture system. They also stimulated interferon (IFN) production, active against HIV-1 and vesicular stomatitis virus (VSV) cytopathic effects. The results suggest that these extracts contain novel anti-HIV active compounds which, individually or in combination, can exert several distinct suppressive effects. The test extracts appear to act specifically at the level of CD4-gp120 binding.     

Anti-HIV-1 protease- and HIV-1 integrase activities of Thai medicinal plants known as Hua-Khao-Yen

Ethanolic- and water extracts from five species of Thai medicinal plants known as Hua-Khao-Yen were tested for their inhibitory effects against HIV-1 protease (HIV-PR) and HIV-1 integrase (HIV-1 IN). The result revealed that the ethanolic (EtOH) extract of Smilax corbularia exhibited anti-HIV-1 IN activity with an IC50 value of 1.9 microg/ml, followed by the water extract of Dioscorea birmanica (IC50 = 4.5 microg/ml), the EtOH extract of Dioscorea birmanica (IC50 = 4.7 microg/ml), the water extract of Smilax corbularia (IC50 = 5.4 microg/ml), the EtOH extract of Smilax glabra (IC50 = 6.7 microg/ml) and the water extract of Smilax glabra (IC50 = 8.5 microg/ml). The extracts of Pygmaeopremna herbacea and Dioscorea membranacea were apparently inactive (IC50 > 100 microg/ml). Interestingly, only the EtOH extract of Dioscorea membranacea showed appreciable activity (IC50 = 48 microg/ml) against HIV-1 PR, while the other extracts possessed mild activity. This result strongly supported the basis for the use of Smilax corbularia and Dioscorea membranacea for AIDS treatment by Thai traditional doctors.     

Phenolic‐Linked Biochemical Rationale for the Anti‐Diabetic Properties of Swertia chirayita (Roxb. ex Flem.) Karst.

The crude extract of Swertia chirayita, an important medicinal plant of Nepal, is locally used for many diseases including type 2 diabetes. In this study, crude aqueous and 12% ethanol solution extracts of S. chirayita collected from nine districts of Nepal were analyzed for anti‐diabetic‐linked anti‐hyperglycemia potential using in vitro biochemical assays. There was moderate‐to‐high positive correlation between antioxidant activity and total phenolic content of both extracts and moderate‐to‐high α‐glucosidase inhibitory activity. Although the anti‐diabetic property of S. chirayita is mainly attributed to the phytochemical swerchirin present in its hexane fraction, we propose that the crude extract of this plant used in local healing also has anti‐hyperglycemia potential. The crude extracts indicated the presence of three main phytochemicals mainly mangiferin, swertiamarin, and amarogentin and their derivatives. Among the standard compounds (mangiferin, swertiamarin, and amarogentin), mangiferin showed α‐glucosidase and 2,2‐diphenyl‐1‐picrylhydrazyl radical inhibitory activity indicating anti‐hyperglycemia potential. Copyright © 2012 John Wiley & Sons, Ltd.     

Antimycobacterial activity of Juglans regia, Juglans mollis, Carya illinoensis and Bocconia frutescens

Mycobacterium tuberculosis is a serious worldwide health threat, killing almost 2 million people per year. Alternative antimycobacterial drugs are urgently needed; studies have shown that medicinal plants traditionally used to treat respiratory diseases are a potential source of compounds to treat tuberculosis. This paper studied the antimycobacterial activity of 28 extracts from four different plant species that have been used in traditional Mexican medicine to treat tuberculosis. Bark and leaf crude extracts of Juglans regia L., Juglans mollis Engelm., Carya illinoensis (Wangenh) K. Koch and Bocconia frutescens showed in vitro anti-M. tuberculosis activity. Hexane bark extracts from C. illinoensis, J. mollis and J. regia were the most active with a minimal inhibitory concentration (MIC) of 31, 50 and 100 microg/mL, respectively. Ethanol bark extracts from C. illinoensis and J. mollis showed activity at 100 and 125 microg/mL, respectively. Leaf extracts had the lowest activity. Methanol and hexane leaves extracts from B. frutescens had a MIC of 125 microg/mL. None of the aqueous extracts showed antimycobacterial activity.     

Identification of antibacterial principles against Streptococcus mutans and inhibitory principles against glucosyltransferase from the seed of Areca catechu L

During the course of our studies on dental caries prevention by traditional medicines, fatty acids (myristic and oleic acids etc.) and procyanidins from betel nuts (the seed of Areca catechu L.) were respectively revealed to be the major antibacterial principles against a primary cariogenic bacterium, Streptococcus mutans, and the major inhibitory principles against glucosyltransferase from S. mutans.     

Inhibitory effects of various ayurvedic and Panamanian medicinal plants on the infection of herpes simplex virus-1 in vitro and in vivo

Extracts of 40 Ayurvedic medicines and 39 Panamanian medicinal plants were screened for their inhibitory activity on the plaque formation of herpes simplex virus type 1 (HSV-1) in cultured cells. The extracts of 11 plant species showed potent inhibitory activity at a concentration of 100 μg/mL, while those of ten species showed moderate activities. Repeated oral administration of each extract of Rhus acuminata (galls), Saraca indica (bark), Strychnos potatrum (seeds) appreciably suppressed the development of typical skin lesions induced by infection of HSV-1 in BALB/c mice. The extract of S. potatrum prolonged both development of skin lesion and mean survival time. This indicates that S. potatrum is a possible candidate for therapeutic application for HSV-1 infection.     

Antiviral activity of chilean medicinal plant extracts

Chilean flora is a potential source of bioactive compounds, including some with antiviral activity. Ninety aqueous and hydroaloholic extracts from 36 native and introduced plant species were screened for antiviral activity on herpes (HSV-1 and HSV-2) and HIV viruses. Furthermore, the samples were assayed for antimicrobial effect on pathogenic bacteria and a yeast. Plants were selected according to their indication of use for treating symptomatology of possible viral aetiology in Chilean folk medicine. The hydroaloholic extracts of Cassia stipulacea and Escallonia illintia exhibited detectable antiviral effects towards HSV-1 with IC₅₀ values of 80 and 40 μg crude extract/mL, respectively. Samples belonging to Aristotelia chilensis (IC₅₀ of 40 μg/mL), Drymis winteri (IC₅₀ values of 35 and 80μg/mL), Elytropus chilensis and Luma apiculata, with an IC₅₀ value of 100 μg/mL showed activity against HSV-2. None of the extracts showed activity against HIV at extract concentrations which were nontoxic for cells.