Acquired immune deficiency syndrome (AIDS) occurs due to infection caused by human immune deficiency virus (HIV). This infection causes immune suppression in the body. It is a serious and life‐threatening condition that affects many people. According to UN-AIDS and WHO recent report in Global HIV and AIDS Statistics‐2018 Fact Sheet, by the end of 2017 worldwide 36.9 Million people were living with HIV and among them only 21.7 Million people were accessing the antiviral therapy. Since the start of the HIV epidemic, a total of 78 million people have become infected with this disease. Those living in Sub‐Saharan Africa are largely affected by this disease. In AIDS, the patients are at significant risk of contracting a wide range of life‐threatening opportunistic infections as well as developing cancers due to the destruction of the human immune system and it was estimated that the life span without treatment after the infection of HIV decreased to 9–11 years, depending on the HIV sub-type.
ROLE OF MEDICINAL PLANTS IN HUMAN IMMUNODEFICIENCY VIRUS HIV
Acquired immune deficiency syndrome (AIDS) occurs due to infection caused by human immune deficiency virus (HIV). This infection causes immune suppression in the body. It is a serious and life‐threatening condition that affects many people. According to UN AIDS and WHO recent report in Global HIV and AIDS Statistics‐2018 Fact Sheet, by the end of 2017 worldwide 36.9 Million people were living with HIV and among them only 21.7 Million people were accessing the antiviral therapy. Since the start of the HIV epidemic, a total of 78 million people have become infected with this disease. Those living in Sub‐Saharan Africa are largely affected by this disease. In AIDS, the patients are at significant risk of contracting a wide range of life‐threatening opportunistic infections as well as developing cancers due to the destruction of the human immune system and it was estimated that the life span without treatment after the infection of HIV decreased to 9–11 years, depending on the HIV sub-type.
The main targets of HIV infections are the vital immune cells like T helper cells (specifically CD4+ T cells), dendritic and macrophages cells. After the infection of these immune cells destruction through a wide range of mechanisms especially of CD4+ T cells occurred like T helper cells become prone to pyroptosis, uninfected bystander cells apoptosis, killing of the cells with direct viral infection, and destructive role played by CD8+ cytotoxic lymphocytes on recognizing the infected CD4+ T cells. Due to multiple mechanisms the lower level of CD4+ T cell make immunocompromised due to loss of cell‐mediated immunity and make the HIV patient more susceptible towards multiple opportunistic infections, finally to develop AIDS.
Currently, Anti‐HIV therapies (ART) are available which have improved the quality of life as well as life span of HIV/AIDS patients. However, ART is associated with serious side effects like lipodystrophy causing peripheral fat loss and central fat accumulation leading thin facial pads, thin legs and arms, buffalo humps and pot bellies and leaving the patient stigmatized. In addition, antiviral drugs have many other disadvantages including the shortage of availability, resistance, toxicity and very low curative effects. Limitations in ART programs continued to find out more potent anti‐HIV drugs.
It has been reported that medicinal plants have significantly high antiviral potential and herbal medicine proved very effective for the treatment of AIDS. It is stated that 44.3% of HIV patients in Australia reported the use of a marijuana compound for therapeutic purposes. Patients have been using medicinal plants as they feel more relaxed, less pain, less stress, spiritualism and greater well‐being. It was reported that approximately, 9% of outpatients believed that it was possible to treat HIV by taking herbs, while some consider that herbs also improved energy level. However, a study conducted in the US reported the commonly treated conditions using herbal medicine are anxiety, depression, fear, pain and nervousness. Although a number of reports are available on folkloric uses of medicinal plants to manage some diseases, knowledge of herbal remedies used to treat HIV/AIDS is limited, impressionistic and not well documented. Medicinal plants contain novel anti‐HIV compounds. It has been well reported that medicinal plants contain various types of phytochemical constituents including alkaloids, flavonoids, phenolic compounds, glycosides, tannins, and saponins. So the medicinal plants could be potential sources of boosting immune responses, as well as halting the replication of HIV. Furthermore, it is important to search for novel antiretroviral compounds that can replace or be added to the present arsenal of drugs against HIV/AIDS. A literature survey of medicinal plants with anti‐HIV property is an important prerequisite to search the novel antiviral agents for the treatment of HIV/AIDS worldwide. Therefore, the effort has been made to review the taxonomic families and species of plants with anti‐HIV active compounds and their modes of action. Bioactive compounds from plants which play effective roles in the management of AIDS are also discussed in this review study.
Anti‐HIV activity of medicinal plants has been reviewed from the published literature by searching reference materials through various databases/search engines and is listed below
Vernonia amygdalina is a shrub used as a traditional herbal medicine for the treatment of HIV/AIDS. It belongs to family Asteraceae and common name of the plant is bitter leaf due to its bitter taste. The studies reported that Vernonia amygdaline has antioxidant activity in HIV positive patients when compared with the commercially available tablet Immunace. V. amygdalina has nutritional and health improving properties. Studies reported the effect of V. amygdalina leaf extract on HIV‐infected patients and those taking antiretroviral therapy. Aqueous extracts of fresh leaves of V. amygdalina were used along with ART to evaluate the effect of herbs on CD4+ cells count for a period of four months. The study results showed that
CD4 count was increased in patients who used the leaf extract or supplements. Those clients who used both supplements and leaf extract had an increase in CD4 count. When compared with the control group, CD4 cell count was found to have increased. Moreover, these patients also recover skin rashes. Leaves of V. amygdalina have an immunological effect on HIV‐infected patients and are used in HIV management. CD4 count depends on the white blood cell count. CD4 cells reduced to low level in HIV phase, being unable to compete with infections. Leaves of fresh bitter leaf are effective for the treatment of persistent fever, headache and joint pain in AIDS patients. Vernonia amygdalina also act as a nutritional supplement.
It has been reported that extracts from Rheum species including Rheum palmatum L. and Rheum officinale Baill contain phytochemical constituents which specifically inhibit the replication of HIV. Esposito et al,21 isolated and investigated the anti‐HIV activity of anthraquinone derivatives on both HIV‐1 reverse transcriptase (RT)‐ associated DNA Polymerase (RDDP) and Ribonuclease H (RNase H) activities in biochemical assays. Then HIV‐1 mutated RTs, integrase (IN) and viral replication as anti‐HIV parameters were also tested to explore the new treatment strategies. Results revealed that HIV‐1 RT‐associated RNase H function is inhibited by the extracts of both R. palmatum L. and R. officinale Baill. Further, studies revealed that Sennoside A and B were the phytoconstituents responsible to inhibit both RDDP and RNase H RT‐associated functions. When SennosideA was studied more, it was noted that there are two RT binding sites for its antiviral activity. Moreover, cell‐based analysis revealed that Sennoside A affects the HIV‐1 replication as well as in vitro studies revealed the phytochemical effects on HIV‐1 IN activity. Viral transcription process is the major target for Sennoside A reported at the time of Viral DNA production.
Trigonostem xyphophylloides and Vatica astrotricha
To explore the inhibitory effects of medicinal plants on HIV‐1, extracts from two traditional Chinese medicinal plants, Trigonostem xyphophylloides (TXE) and Vatica astrotricha (VAD), were investigated. Results revealed that both extracts had few side effects on the multiplication
of host immune cells and their survival significantly halted the replication of HIV‐1 and syncytia formation in CD4+ Jurkat cells. Further, research revealed that TXE and VAD extract have no HIV‐1 RT enzyme inhibitory effects. Treatment with both extracts demonstrated
that TXE and VAD extract have anti‐HIV potential by inhibiting the HIV multiplication and the entry of this virus into target cells. Molecular studies revealed that phytochemical constituents
block the HIV‐1 interaction with target cells, i.e., the interaction between gp120 and CD4/CCR5 or gp120 and CD4/CXCR4 and point to the potential of developing these two extracts to be HIV‐ 1 entry inhibitors.
Hypoxis hemerocallidea is also known as the African potato and belongs to the family Hypoxidaceae. African potato is commonly used as an immune booster. Active ingredients of plants which have anti‐ HIV activity include phytosterols, hypoxide, aglycone and rooperol. African primary health care communities used the root of H. hemerocallidea as an immunostimulant in HIV/AIDS patients and have significant potential to enhance immunity.
The flowering shrub of Sutherlandia frutescens, also called insiswa, belongs to family Fabaceae. L‐canavanine is one of the chemical constituent of S. frutescens which has antiviral activity. 95% of HIV‐infected lymphocytes were selectively destroyed in vitro. It has been reported that a daily dose of 9 mg/kg/d is effective to stimulate the immune system in infective persons but further investigations are needed to explore the mechanism of actions of phytochemicals present this medicinal plant.
Hypericum perforatum L
Also known as St. John’s Wort, Hypericum perforatum belongs to the plant family Hypericaceae. It has been used for medicinal purposes in traditional medicinal system particularly for wound healing and also for the treatment of AIDS. The antiretroviral activity of phytoconstituents like hypericin and pseudohypericin isolated from H. perforatum in HIV‐infected patients have been observed during a clinical trial.
This plant belongs to the Polyporaceae family. The hexane extract of this plant used in Korean folk medicine has shown anti‐HIV‐1 activity. The plant extract also showed the protective effect on infected MT‐4 cells and the highest protection was observed at 58.2%. The 50% cytotoxic concentration (CC50) of Pachymahoelen hexane extract was found 100.6 μg/mL.
Terminalia paniculata belongs to Combretaceae plant family. The in vitro anti‐HIV‐1 activity of T. paniculata fruits extract prepared in methanol and acetone solvent was tested and the EC50 values of this plant extracts in acetone and methanol were ≤10.3 μg/mL. The mechanism of action was determined through enzymatic assays which indicated the anti‐HIV‐1 activity due to the inhibition of protease (≥69.9% inhibition) and reverse transcriptase (≥77.7% inhibition) enzymes.18,35
Smilax corbularia Kunth
Smilax corbularia belongs to the plant family Smilaceae. The inhibitory effects of ethanolic and aqueous extracts of S. corbularia against HIV‐1 protease (HIV‐PR) and HIV‐1 integrase (HIV‐1 IN) was tested and found that S. corbularia ethanolic extract exhibited anti‐HIV‐1 IN activity with an IC50 value of 1.0 μg/mL and the suramin was used as positive control having IC50 of 3.4 μg/mL. The IC50 value determined for the water extract of this plant was 5.4 μg/mL. The study finding showed a two‐fold lower IC50 value of ethanolic extract of S. corbularia.
Tuberaria lignose Sampaio
Tuberaria lignosa belongs to the Asteraceae plant family. This plant was widely used in traditional medicine for the treatment of viral diseases. The anti‐HIV activity of ethanolic and aqueous extracts of this plant by inhibiting the HIV replication. The study results showed that the tested T. ligosa aqueous extract was relatively nontoxic to human lymphocytic MT‐2 cells without showing anti‐HIV activity between 12.5 and 50 μg/mL concentrations range. The toxicity of ethanolic extract of this plant prevented the evaluation of their potent antiviral activity at increased concentrations.