Journal of Clinical Research in HIV AIDS and Prevention
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  • Phytochemicals May Arrest HIV-1 Progression

    B. Sharma 1      

    1Department of Biochemistry, Faculty of Science,

    Received 02 Dec 2013; Accepted 05 Dec 2013; Published 21 Jan 2014;

    Copyright©  2014 Bechan Sharma, et al.

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    Creative Commons License    This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Competing interests

    The authors have declared that no competing interests exist.

    Citation:

    B. Sharma (2014) Phytochemicals May Arrest HIV-1 Progression. Journal of Clinical Research In HIV AIDS And Prevention - 1(3):1-5.
    Download as RIS, BibTeX, Text (Include abstract )
    DOI10.14302/issn.2324-7339.jcrhap-13-edt.1.3

    Introduction



    The application of current antiretroviral chemotherapeutics such as antiHIV-1 RT drugs (nucleoside, nucleotide and non-nucleotide reverse transcriptase inhibitors) as well as antiproteases including those used in combinatorial therapy such as highly active antiretroviral; (HAART) has caused significant reduction in the rate of mortality of HIV-1 infected individuals. It has allowed sufficient rise in CD4+ve lymphocyte counts into the HIV-1 infected individuals and imparted relatively longer and healthier lives. Recent reports, however, have indicated that application of plant based principles may prove to be highly useful, affordable and efficient in order to arrest the HIV-1 progression. It may be accelerative in transition from development to usage. Also, the toxicity issues may be easily managed while treating AIDS patients with herbal preparations as these plant-ingredients are suitably metabolized and excreted out of body without much accumulation in human organs. Certain plant extracts such as green tea containing ((-)-Epigallocatechin-3-gallate (EGCG)), Brazil nut and Caocao containing immunopotentiators, grapes and red wine containing plenty of antioxidants which mimic oxidative stress induced by intake of antiHIV-1 regimen, Punica granatum (pomegranate) and several others have been recently shown to possess properties of intervention in HIV-1 proliferation 1. The aqueous and ethanolic extracts of Phyllanthus amarus exhibits potential to inhibit the replication of even antiHIV-1 drug resistant variants in different ways viz., by blocking the interaction of gp120 with its primary cellular receptor CD4 as well as inhibition of activities of HIV-1 integrase, reverse transcriptase and protease enzymes (Frank et al., 2004). The ethanol extract of Nelumbo nucifera Gaertn. (Kamal) 2 as well as Pine Cone extract from Pinus yunnanensis 3 have been shown to contain some molecules which in isolation or in combination display strong antiHIV-1 activity. There are also sporadic reports that medicinal herbs can act as phytochemical therapy in the control of AIDS 4, 5. It has been suggested by some workers that the bioactive compounds in the medicinal herbs work in coordination rather than in tandem in the restoration of the health of AIDS patients. Their mechanism of action, however, may vary to certain degrees 4, 5. This article presents a current account of reports available on phytochemicals isolated from various parts of different plant species which exhibit strong capability to block HIV-1 activity. These molecules possess immense possibility to be developed as potential antiHIV-1 chemotherapeutics in future. Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that causes Acquired Immunodeficiency Syndrome (AIDS), a condition in humans in which the immune system begins to fail, inviting various life-threatening opportunistic infections 6, 7. When HIV enters the human body, its target is a subset of T-lymphocyte immune cells that contain CD4 receptors 5.

    All the antiHIV-1 drugs available to date to treat AIDS patients target HIV-1 reverse transcriptase (RT) and protease (PR). HIV-1 RT is responsible to catalyse the synthesis of complementary double stranded DNA (cDNA) which is later integrated into the human genome. HIV-1 protease (HIV-1 PR), on the other hand, catalyses the cleavage of the polyprotein chain synthesized on the viral transcript into specific viral components leading to maturation of the virus. HIV remains uninfectious because its work 8. HIV-1 PR thus acts a promising target for therapy of the HIV infection. Unless the HIV life cycle is interrupted by specific treatment, the virus infection spreads rapidly throughout the body, which results in the weakness and destruction of the body’s immune system 9.

    Treatment of HIV/AIDS is limited due to unavailability and high costs of antiretroviral drugs (ARVs) together with limited infrastructure for monitoring of HIV/AIDS patients. Other factors adversely affecting the treatment include rapidly emerging drug resistance and toxicity 10, which has always been a challenge to physicians for chemotherapy. The involvement of host cellular factors in viral progression makes the situation more complex 11. To overcome these issues to the greater extent, the quest for new, effective and safe as well as affordable anti-HIV agents is a necessity 12. Some alternative and complimentary medicines are being explored worldwide. Phytomedicines have shown great promise in the treatment of infectious diseases including AIDS-related opportunistic infections 13. The pool of existing information indicate that the majority of traditional healers in Eastern, Southern and Western Africa use Combretaceae species for treatment of several medical conditions include respiratory diseases, sex-linked diseases, cancer, gastrointestinal and stress related disorders, parasitic, zoonotic and viral diseases including HIV-1 infections etc. 14, 15, 16, 17.

    Plants of the Combretum and Terminalia genera constitute majority of the Combretaceae family that are widely represented in Tanzania. At least 55 and 17 species of Combretum and Terminalia, respectively, are reported to be growing in Tanzania ranging from climbers, shrubs and big trees 18. Most of these species are also found in other parts of tropical and warm temperate regions of the world 16, 18. Combretum adenogonium Steud. Ex A. Rich (Combretaceae) (syn: Combretum fragrans F. Hoffm or Combretum ghasalense Engl. & Diels) is a shrub or a small tree which grows up to 10-12 m high 18, 19. In various parts of Africa, the plant is used for treatment of several clinical conditions such as leprosy, cough and syphilis, snakebite, aphrodisiac, diarrhea, new and chronic wounds, malaria and even septic wounds and fungal infection of the scalp 20, 21. Root, leaf and stem bark extracts of this plant have been investigated and established as having antifungal 22, 23, 24, antibacterial 25 and antiproliferative (Fyhrquist et al., 2006) 20 properties. Stem bark of C. adenogonium have shown to exhibit significant Clostridium chauvoei neuraminidase enzyme inhibitory activity 26. Previous phytochemical analyses have shown that, extracts of stem barks, root and leaves of C. adenogonium contain flavonoids, tannins and few saponins 22, 27. Furthermore, chemical analyses have shown that two phytosterols (β-sitosterol and stigmasterol) were isolated from the stem bark of C. adenogonium 28. The extracts of C. adenogonium were found to contain antibacterial and anti HIV-1 protease activities but these extracts also exhibit some cytotoxic properties. After removing the cytotoxic constituents, these preparations may be used in managing HIV and AIDS-related opportunistic infections 29, 30.

    Aqueous ethanolic extracts of root and stem bark of C. adenogonium have exhibited moderate anti-HIV-1 protease inhibitory activity with IC50 value in higher μg range as compared to that of the acetyl pepstatin, a positive control, with an IC50 value of 2.2 μg/ml 24. The anti-HIV-1 activity of C. adenogonium and its use in managing HIV/AIDS diseases is well supported by other species of Combretaceae 20, 24, 29, 30, 31.

    It is important to note that a number of promising anti-HIV natural products have made it to the clinical level and are anticipated to be available to patients very soon 12. The following natural products can be cited as promising anti-HIV agents of plant origin: baicalin (a flavonoid) 32 , calanolides (coumarins) 32, betulinic acid (a triterpene) 33, 34, polycitone A (an alkaloid) 35, lithospermic acid, sulphated polysaccharides, cyanovirin-N 36, pokeweed antiviral protein 37 and alpha-trichobitacin (proteins). Phytochemical screening of the extracts indicated presence of flavonoids, terpenoids, alkaloids, tannins, glycosides and saponins 38.

    Punica granatum (pomegranate) juice can act as an HIV-1 entry inhibitor. Neurath and coworkers (2005) 39 screened the fruit juices for their inhibitory activity against HIV-1 IIIB using CD4 as cell-receptor and CXCR4/CCR5 as cell co-receptors and reported that the juice of pomegranates contain the constituents with potential to inhibit HIV-1 progression by blocking its entry into the CD4+ve lymphocytes. The inhibitory property of this preparation was also found for infection by primary virus clades A to G and group O. This fruit juice also exhibits significant microbicidal properties; which is expected to block the cell to cell transmission of viruses. Their results indicated the possibility of producing a safe and cost effective anti-HIV-1 microbicide from pomegranate in future. They have proposed the mechanism of inhibition via arresting the docking process between the primary virus clades and the corresponding lymphocytes 39.

    The green tea constituents have potential to block HIV-1 progression. Zhang et al (2012) 40 have investigated the effects of ((-)-Epigallocatechin-3-gallate (EGCG)), a chemical component isolated from green tea on Tat-induced HIV-1 transactivation and reported that EGCG inhibited activation of NF-κB pathway. EGCG inhibited Tat-induced long terminal repeat (LTR) transactivation process in a dose-dependent manner. Nrf2 signaling pathway may be the primary target for prevention of Tat-induced HIV-1 transactivation by EGCG 40. Similarly, the potent anti-HIV activities and mechanisms of action of a pine cone extract from Pinus yunnanensis has also been proposed by other workers 41.

    The Anti-HIV and immunomodulation activities of cacao mass lignin-carbohydrate complex have been displayed. Cacao mass LCC and LPS may synergistically stimulate iNOS protein expression, suggesting a different point of action. Cacao mass LCC induces tumour necrosis factor-α production markedly less than LPS, and does not induce interleukin-1β, interferon-α or interferon-γ. ESR spectroscopy showed that cacao mass LCC, but not LPS, scavenged NO produced from NOC-7 42. Further, the skin and seed of grapes, berries, peanuts and red wine containing resveratrol, a polyphenolic plant-derived antioxidant, indicated that this molecule protected the AZT induced concentration-dependent cell death 43. The AZT-induced cell death has been reported to involve both caspase-3 and -7 and poly(ADP-ribose) polymerase activation, coupled with increased mitochondrial ROS generation in human cardiomyocytes 44, 45.

    The limited information available as mentioned above indicates that there is lot of potential in the natural products isolated from certain medicinal plants to use against HIV-1 infected individuals, which could be cost effective, safe and easily accessible to the AIDS patients. However, still more efforts are required to be made by researchers in this direction to find out a reliable natural product for AIDS treatment, though it can not be presumed anything now on the issue that the application of natural products would be able to block the progression of wild type and drug resistance virions without inducing another drug-resistance variants by way of generating new mutations.

    References

    1.Sharma B. (2013) Phytochemicals as antiHIV-1 tools. Proceedings of international conference and exhibition on biochemical and molecular engineering. Omics Group. October 7-9, 2013 , Hilton San Antonio Air Port, USA .
    2.Frank N, George M, Ralf W. (2004) Concerted inhibitory activities of Phyllanthus amarus on HIV-1 replication in vitro and exvivo. , Antiviral Research 64(2), 93-102.
    3.Yoshiki K, Akihiro A, Yasumasa I, Yuh-Pan C, Hiroshi F et al. (2005) AntiHIV benzyl isoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera and structure-activity correlations with related alkaloids. , Bioorganic Medical Chemistry 13(2), 443-8.
    4.F M Uckun, L M Chelstrom, Tuel-Ahlgren L, Dibirdik I, J D Irvin et al. (1998) TXU (Anti-CD7)-Pokeweed Antiviral Protein as a Potent Inhibitor of Human Immunodeficiency Virus. Antimicrob Agents Chemother. 42, 383-8.
    5.Seal A, Aykkal R, Babu R O & Ghosh, M. (2011) Docking study of HIV-1 reverse transcriptase with phytochemicals. , Bioinformation 5(10), 430-39.
    6.Douek D C, Roederer M, Koup R A. (2009) Emerging concepts in the immunopathogenesis of AIDS. , Annual Reviews in Medicine 60, 471-8.
    7.Weiss R A. (1993) How does HIV cause AIDS. , Science 260, 1273-9.
    8.Sanjay K. (2010) Gene (HIV-1 protease) based drug (inhibitor) Discovery. , Journal of Advanced Bioinformatics Applications and Research 1, 17-26.
    9.Ramalingam M, Karthikeyan S, Kumar D. (2012) . Docking Studies of HIV-1 Protease with Phytochemicals from Mappia Foetida , International Journal of Computer Applications 43(4), 16-22.
    10.Sharma B. (2011) The antiHIV-1 drugs toxicity and management strategies. , Neurobehavioural HIV Medicine 3, 1-14.
    11.Sharma B. (2012) Attributes of Host’s Genetic Factors in HIV-1 Pathogenesis. , Biochemical and Analytical Biochemistry 1, 4-7.
    12.Asres K, Seyoum A, Veeresham C, Bucar F, Gibbons S. (2005) . , Phytotherapy Research 19(7), 557-581.
    13.Iwu M M, Duncan A R, Okunji C O. (1999) New Antimicrobials of Plant Origin. In Perspectives on newcrops and new uses. Edited by Janick J. , Alexandria, VA:ASHS,Press;1999
    14.J N Eloff, Katerere D R & McGaw, J L. (2008) The biological activity and chemistry of the southern African Combretaceae. , Journal of Ethnopharmacology 119, 686-99.
    15.Koudou J, Roblot G, Wylde R. (1995) Tannin Constituents of Terminalia glaucescens. Planta Med. 61, 490-491.
    16.L J McGaw, Rabe T, S G, A K Jager, J N Eloff et al. (2001) An investigation on the biological activity of Combretum species. , Journal of Ethnopharmacology 75(1), 45-50.
    17.Masoko P, Picard J, Eloff. (2005) Antifungal activities of six South African Terminalia species (Combretaceae). , Journal of Ethnopharmacology 99, 301-8.
    18.G E Wickens. (1973) Combretaceae. In Flora of Tropical East Africa. Edited by Polhill RM. London: Crown Agents for Oversea Governments and Administrations;1973.
    19.Steud Ex A Rich. (2012) (Combretaceae) BMC Complementary and Alternative Medicine. 12-163.
    20.Fyhrquist P, Mwasumbi L, Hæggström C-A, Vuorela H, Hiltunen R et al. (2006) Ethnobotanical and antimicrobial investigation of some species of Terminalia and Combretum (Combretaceae) growing in Tanzania. , Journal of Ethnopharmacology 79, 169-77.
    21.S M Maregesi, O D Ngassapa, Pieters L, A J Vlientinck. (2007) Ethnopharmacological survey of the Bunda district, Tanzania: Plant used to treat infectious diseases. , Journal of Ethnopharmacology 113, 457-70.
    22.Batawila K, Kokou K, Koumaglo K, Gbe'assor M, Foucault D et al. (2005) Antifungal activities of five Combretaceae used in Togolese traditional medicine. , Fitoterapia 76, 264-8.
    23.Fyhrquist P, Mwasumbi L, Hæggström C-A, Vuorela H, Hiltunen R et al. (2004) . Antifungal Activity of Selected Species of Terminalia, Pteleopsis and Combretum(Combretaceae) Collected in Tanzania. Pharm Biol,42(4–5) 308-17.
    24.Maregesi S, S Van Miert, Pannecouque C, Feiz Haddad MH, Hermans N et al. (2009) Screening of Tanzanian medicinal plants against Plasmodium Faliciparum and Human immunodeficiency virus. , Planta Med 75, 1-7.
    25.S M Maregesi, Pieters L, O D Ngassapa, Apers S, Vingerhoets R et al. (2008) Screening of some Tanzanian medicinal plants from Bunda district for antibacterial, antifungal and antiviral activities. , Journal of Ethnopharmacology 119, 58-66.
    26.N M Useh, A J Nok, S F Ambali, Esievo K A N. (2004) The Inhibition of Clostridium chauvoei (Jakari strain) Neurarninidase Activity by Methanolic Extracts of the Stem Barks of Tamarindus indicus and Combretum fragrans. , Journa1 of Enzyme Inhibition and Medicinal Chemistry 19(4), 339-42.
    27.S C Chhabra, F C Uiso. (1990) A survey of the medicinal plants of Eastern Tanzania for Alkaloids, flavonoids, saponins and tannins. , Fitoterapia 61, 4.
    28.A O Maima, G N Thoithi, S N Ndwigah, F N Kamau, I O Kibwage. (2008) Phytosterols from the stem bark of. , Combretum fragrans F. Hoffm. East and Central African Journal of Pharmaceutical Sciences 11, 52-5.
    29.Tewtrakul S, Miyashiro H, Nakamura N, Hattori M, Kawahata T et al. (2003) HIV-1 intergrase inhibitory substances from Coleus parvifolius. , Phytother Res 17, 232-9.
    30.Tewtrakul S, Subhadhirasakul S, Kummee S. (2003) HIV-1 protease inhibitory effects of medicinal plants used as self medication by AIDS patients. , Songklanakarin Journal of Science and Technology 25, 239-43.
    31.Kisangau D P, HVM Lyaruu, Hosea K M, Joseph C C. (2007) Use of traditional medicines in the management of HIV/AIDS opportunistic infections in Tanzania: a case in the Bukoba rural district. , Journal of Ethnobiology Ethnomedicine 3, 29.
    32.Kitamura T, Sekimata M, Kikuchi S, Homma Y. (2005) Involvement of poly (ADP-ribose) polymerase 1 in ERBB2 expression in rheumatoid synovial cells. , American Journal of Physiology and Cell Physiology 89(1), 82-8.
    33.R H Cichewicz, S A Kouzi, R H Cichewicz, S A Kouzi. (2004) Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. , Medical Research Review 24, 94.
    34.Zhou P, Takaishi Y, Duan H, Chen B, Honda G et al. (2000) Anti-HIV potential of medicinally important plants. , Phytochemistry 53, 689-97.
    35.S L Holz-, I C Sun, Jin L, T J Matthews, K H Lee et al. (2001) Role of human immunodeficiency virus (HIV) type 1 envelope in the anti-HIV activity of the betulinic acid derivative IC9564. , Antimicrob Agents Chemotherapy 45, 60-6.
    36.Loya S, Rudi A, Y A Kashman. (1999) Polycitone A, a novel and potent general inhibitor of retroviral reverse transcriptases and cellular DNA polymerases. , Biochem J 344, 85.
    37.Dey B, D L Lerner, Lusso P, M R Boyd, J H Elder et al. (2000) Multiple antiviral activities of cyanovirin-N: blocking of human immunodeficiency virus type 1 gp120 interaction with CD4 and coreceptor and inhibition of diverse enveloped viruses. , Journal of Virology 74, 4562-9.
    38.Mushi N, Z H Mbwambo, Innocent E, Teutrakul S. (2012) Antibacterial, anti-HIV-1 protease and cytotoxic activities of aqueous ethanolic extracts from Combretum adenogonium Steud. Ex A. Rich (Combretaceae). , BMC Complementary and Alternative Medicine 12, 163-9.
    39.A R Neurath, Strick N, Li Y Y, Debnath A K. (2005) Punica granatum (pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide. Annals of New York Academy of. Sciences,1056 311-27.
    40.Zhang H S, Wu T C, Sang W W, Ruan Z. (2012) . EGCG inhibits Tat-induced LTR transactivation: role of Nrf2, AKT, AMPK signaling pathway. Life Sciences 90, 747-54.
    41.Zhang X, Yang L-M, Liu G-M, Liu Y-J, Zheng C B et al. (2012) Potent Anti-HIV Activities and Mechanisms of Action of a Pine Cone Extract from Pinus yunnanensis. , Molecules 17(6), 6916-29.
    42.Sakagami H, Kawano M, Thet M M, Hashimoto K, Satoh K et al. (2011) Anti-HIV and immunomodulation activities of cacao mass lignin-carbohydrate complex. , In Vivo 25(2), 229-236.
    43.R Y Gao, Mukhopadhyay P, Mohanraj R, Wang H, Horváth B et al. (2011) Resveratrol attenuates azidothymidine-induced cardiotoxicity by decreasing mitochondrial reactive oxygen species generation in human cardiomyocytes. , Molecular Medicine Report 4(1), 151-5.
    44.S K Prakash. (2010) Status of hiv-1 proviral dna with the treatment of poly phytochemical molecules. , International Journal of Pharma and Bio Sciences 1, 2-2010.
    45.S K Prakash. (2011) Eradication of HIV in association with treatment of phyto-Antiviral regimen. , International Journal of Pharma World Research 1(2), 1-15.