South African Journal of Botany 129 (2020) 272–282

Contents lists available at ScienceDirect

South African Journal of Botany

journal homepage: www.elsevier.com/locate/sajb

Moringa oleifera Lam. and derived phytochemicals as promising antiviral

agents: A review
D. Biswas a, S. Nandy a, A. Mukherjee b, D.K. Pandey c,⁎, A. Dey a,⁎
a
Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, West Bengal, India
b
MMHS, South 24 Pgs, West Bengal, India
c
Department of Biotechnology, Lovely Faculty of Technology and Sciences, Lovely Professional University, Phagwara, Punjab, India

a r t i c l e i n f o a b s t r a c t

Article history: Frequent use of medicinal plants is common in healthcare needs of mankind since ancient ages. Among these
Received 26 March 2019 Moringa oleifera Lam. is one of the vastly used plant whose various parts (leaf, fruit, seeds etc.) are included in
Received in revised form 12 July 2019 regular diet for their multiple ability of combating several health issues. WHO has highlighted on the proper
Accepted 29 July 2019
utilization of natural products and marked plant-based medicines as prime study candidates. Taking initiative
Available online 19 August 2019
to explore bioactive leads other than conventional chemotherapeutic agents (with undesirable side effects)
Edited by NE Madala have drawn attention of the scientists involved in viral research due to the lack of effective vaccines and insuffi-
cient supply of existing costly drugs to socio-economic demands. Several studies were reported regarding the an-
Keywords: tiviral activity of M. oleifera plant, a pronounced bioprospective aspirant. The plant is known to be used in many
Medicinal plant traditional medicines and pharmacopeias against an array of medical conditions that include malaria, diabetes,
Moringa oleifera skin infection, tuberculosis, anemia, headaches, epilepsy, sexually transmitted diseases and so on. In African tra-
Antiviral activity ditional medicine, the plant is popularly used against AIDS and related secondary infections associated with HIV.
Viral targets It showed significant activities against viruses like HIV, HSV, HBV, EBV, FMDV and NDV. In some cases active mol-
Clinical trials
ecules with mode of actions were documented by authors. On the other hand, there is a number of reports where
neither lead compounds nor the relevant mechanisms were clarified regarding the viral inhibitory activities of
crude plant extract. Immense studies should be going on to resolve those unanswered motifs along with the
well planned trials of clinical application of already discovered potent phytochemicals. For conducting the contin-
uous investigational groundwork in this field, the respective plant should be preserved with proper maintenance,
necessarily.
© 2019 SAAB. Published by Elsevier B.V. All rights reserved.

1. Introduction (Flora and Pachauri, 2011). Ayurveda advocates its use for pain relief
and rapid expulsion of worms (Khan and Balick, 2001). In Ayurveda,
Plants are rich source of secondary metabolites and have been used the leaves of the plant are rubbed on a flat stone with water is being
for a variety of therapeutic purposes since the early days of human civ- added gradually (Rathi et al., 2006). Traditional African diet recognizes
ilization. From ancient time to modern era of research, plant-derived the leaves, pods, seeds and flowers of the plant as prolific source of
natural moities have shown great contribution in the field of treating nutrition as well as “Miracle Tree” against a number of chronic human
several ailments with their pharmaceutical potentials. Moringa oleifera diseases (Matic et al., 2018). The plant is known as Haritashaaka,
Lam. (Moringaceae), commonly known as “drumstick tree,” an impor- Raktaka and Akshiva in Ayurveda and as Sahajan in Unani system of
tant medicinal plant belongs to the family Moringaceae under the medicine (Paikra et al., 2017).
order Brassicales, is widely distributed and cultivated throughout the Several years ago, small pox (caused by Variola major and Variola
tropical and subtropical region of South Asia, especially in Indian sub- minor) and chicken pox (caused by Varicella zoster) infections used to
continent. Various parts of this perennial, soft wood plant have long transmit in human in a higher rate with painful symptoms like high
been used for the malnutrition, weakness in pox, antipyretic, diuretics, fever, reddish skin rashes, loss of appetite with severe weakening of
antioxidants, anti-inflammatory, anti-diabetic etc. in traditional healing nervous system. Once upon a time, M. oleifera seeds and flowers were
practices. Moringa oleifera is one plant used in both ancient systems of used for those affected individuals, commonly in some regional culture,
medicine such as Ayurveda and the Chinese ancient medicinal system to push forward immunity development against these type of suffer-
ings. Various parts of this plant have the traditional use in skin problem
⁎ Corresponding authors. (leaves, seeds, root, gum), nervous disorder (leaves, flower, root, bark,
E-mail address: abhijit.dbs@presiuniv.ac.in (A. Dey). gum), immunity imbalance (seeds) etc. as cited in literature (Kuben

https://doi.org/10.1016/j.sajb.2019.07.049
0254-6299/© 2019 SAAB. Published by Elsevier B.V. All rights reserved.
 D. Biswas et al. / South African Journal of Botany 129 (2020) 272–282 273

and Roger, 2016). Scientific reports did not highlight on its direct effect traditional herbal medicines in national health care systems, simulta-
on small pox or chicken pox, formally. Research is not going on regularly neously (WHO, 2013). Ethnobotanical information have provided a bet-
on small pox at present because WHO has declared the world as free ter opportunity of finding active leads easily than that of random
from small pox infection in May, 1980 as no record found about the af- screenning.
fected person after last patient of the respective disease was marked in Therapeutic principles of traditional medicinal plants were found to
Somalia in 1978 (WHO, 1980). Severity of chicken pox is now manage- be efficient in yielding potent antiviral drug molecules and offered
able with antiviral drugs of acyclovir group and effective vaccine was themselves for scientific evaluationowing to the high cost and undesir-
invented a few years ago. In this field, research can be continued on able side effects of conventional antiviral drugs, absence of effective vac-
this plant to discover an alternative remedial measure. cines (in some cases) and emergence of resistant strains. Moringa
Presently, even in well-developed countries, research on this medic- oleifera plant possesses remarkable inhibitory activities against viruses
inal plant has received considerable interest due to its different promis- like HIV (Nworu et al., 2015), HSV (Goswami et al., 2016), HBV
ing bioactivities viz., hepatoprotective (Farooq et al., 2012), antibacterial (Feustel et al., 2017), EBV (Murakami et al., 1998), FMDV (Imran et al.,
(Abraham et al., 2014; Rahman et al., 2009), antifungal (Ganie et al., 2016) and NDV (Okwor et al., 2013) according to the reports of some
2015; Patel et al., 2014), anti-cancerous (Abd-Rabou et al., 2017; authors. The objective of the review is to focus mainly on the potential
Al-Shahrani et al., 2015), anti-inflammatory (Faizal et al., 2014) etc. as antiviral efficacy of this plant along with some brief ideas about the re-
cited in several literatures. Being a good repository of antioxidants spective viruses, epidemiology and conventional therapy till date.
(Vats and Gupta, 2017), M. oleifera plant might be included in regular di- Besides it also presents the traditional use of this popular medicinal
etary supplement for the utilization of its ROS scavenging activity plants as an antiviral agent and also against AIDS and related secondary
needed for faster recovery from pathogen related issues promoted infections associated with HIV especially in the vast areas of the Africa.
through overproduction of oxidants in human body and effect of ROS Table 1 presents traditional medicinal uses of M. oleifera against other
in immune system in the advent of resistant strains. medical conditions and Table 2 presents the traditional use of the
WHO also have declared the necessity to embrace a systematic ap- plant as antiviral agent especially against HIV/AIDS and related second-
proach for the evaluation of phyto-constituents as important resources ary infections associated with HIV.
in generating effective and affordable therapeutic agents with negligible
toxicity (WHO, 2005). WHO is now emphasized on the regulation and
policy development for the inclusion and validation of the use of 2. Methodology

Scientific search engines such as Medline, Google Scholar, PubMed,

Table 1
Traditional medicinal uses of Moringa oleifera against various medical conditions.
Pubget, Scopus, ScienceDirect, SpringerLink, Highware, Mendeley,
EMBASE, JSTOR were critically searched to obtain papers with the help
Locality of use Used against References of search strings viz. “Moringa oleifera,” “Moringa oleifera antiviral,”
Guatemala skin, digestive, respiratory and joint Cáceres et al. “Moringa oleifera HIV/AIDS/HSV/HBV/EVB/FMDV/NDV,” “Moringa
diseases (1991) oleifera traditional,” “Moringa oleifera ethnobotany” etc. Cross-
Nigeria Arthritis, diabetes, fever, asthma, Popoola and
referencing among the obtained papers also retrieved a total number
epilepsy, wound, body pains and Obembe (2013)
weakness, cough, blood pressure, skin of 73 publications from 1980 to 2018 which are cited in the present
infection, chronic anemia, cancer, work. The paper compiles the use of M. oleifera against 6 different vi-
malaria and hemorrhage ruses investigated in 14 research papers. Information presented in this
Nhema communal Diarrhea, toothache Maroyi (2011)
area, Zimbabwe
Batan Island, the Diabetes, anemia, high blood pressure Abe and Ohtani Table 2
Philippines (2013) Traditional use of Moringa oleifera as antiviral agent especially against HIV/AIDS and re-
Limpopo Province, Diabetes mellitus Semenya et al. lated conditions.
South Africa (2012)
Locality of use Used against References
Thoppampatti, Cardiac, circulatory stimulant, Sivasankari
Dindigul district, antipyretic, anthelmintic, antiparalytic et al. (2014) Nigeria HIV/AIDs infections Popoola and
Tamilnadu, India Obembe,
Ogbomoso, Southwest Malaria Olorunnisola (2013)
Nigeria et al. (2013) Southern Benin Nutritional powder to the persons living Agoyi et al.
Ibadan, Nigeria Sexually transmitted infections Gbadamosi with HIV/AIDS (2014)
(2014) Katima Mulilo, HIV/AIDS-related opportunistic infections Chinsembu and
Kimboza forest Skin diseases, headache, detoxification, Amri and Caprivi region, Hedimbi (2010)
reserve in rheumatism, inflammation Kisangau Namibia
Morogoro, Tanzania (2012) Uganda HIV/AIDS and related conditions Lamorde et al.
Rwanda Voluntary depigmentation Kamagaju et al. (2010)
(2013) Keffi Metropolis, HIV/AIDS opportunistic infections Mustapha
Tirunelveli hills of To increase sperm production Ayyanar and Nigeria (2014)
Western Ghats, Ignacimuthu Western Uganda Boost appetite/immunity (management of Asiimwe et al.
India (2011) HIV/AIDS opportunistic ailments) (2013)
Niger State, Nigeria Tuberculosis and other respiratory Mann et al. North-west Diarrhea, skin infections, vomiting Noumi and
diseases (2007) Cameroon (management of HIV/AIDS opportunistic Manga (2011)
Sokoto, Northwest Diabetes Shinkafi et al. ailments)
Nigeria (2015) Katima Mulilo, Diarrhea, skin infections, vomiting Chinsembu and
India and other parts Inflammation, infectious diseases, Morimitsu et al. Caprivi region, (management of HIV/AIDS opportunistic Hedimbi (2010)
of South Asia gastrointestinal, hematological, (2000) Namibia ailments)
cardiovascular and hepatorenal Jos, Plateau state, Antiviral (hepatitis) Ohemu et al.
disorders, tumors, headache, Nigeria (2014)
India, Africa Syphilis, malaria, skin diseases, Gopalakrishnan Uganda HIV/AIDS and related conditions Lamorde et al.
bronchitis, pneumonia, liver and spleen et al. (2016) (2010)
problems, joint pain, diarrhea, Zimbabwe To boost the immune system in HIV/AIDS Monera et al.
headaches, epilepsy and sexually patients (2012)
transmitted diseases, scurvy, gout, Jos, Plateau state, Viral infections Ohemu et al.
cramp Nigeria (2014)
274 D. Biswas et al. / South African Journal of Botany 129 (2020) 272–282

review may be used for basic and clinical research on the antiviral effi- RNA genome of HIV is encapsulated with glycoprotein envelope
cacy of M. oleifera in future. which consists of two subunits named gp120 and gp41. Fusion of
gp120 with the CD4 positive T cell of the host mediates a conforma-
tional change in gp120 and it ensures efficient interactions with cellular
3. Brief idea about viruses inhibited by M. oleifera
factors CCR5 and CXCR4. This results the viral entry into the host cell.
After this, single-stranded RNA genome of HIV is reverse transcribed
Documentation of previous reports have said that the plant M.
into double-stranded DNA molecule by reverse transcriptase and inte-
oleifera (Moringaceae) showed inhibitory activity principally against a
grated into the host genome through the activity of integrase. Subse-
few infectious disease causing viruses viz., (A) Human Immunodefi-
quent polyprotein processing takes place with protease for the
ciency Virus (HIV), causative agent for Acquired Immune Deficiency
maturation and proliferation of virion particles (Kirchhoff, 2013). Sche-
Syndrome (AIDS) in human; (B) Herpes Simplex Virus (HSV) causes
matic representation is given in Fig. 1. Conventional drugs are applied to
fever blisters or cold sores around the mouth and lips and genital infec-
target different components of HIV life-cycle like lamivudin (reverse
tion in human body; (C) Hepatitis B Virus (HBV) which affects human
transcriptase inhibitor), elvitegravir (integrase inhibitor), ritonavir
liver and causes inflammation, cirrhosis and liver cancer; (D) Epstein–
(protease inhibitor), nelfinavir (protease inhibitor), zidovudine (re-
Barr Virus (EBV) responsible for various non-malignant, premalignant
verse transcriptase inhibitor), maraviroc (target CCR5, inhibits entry),
and malignant lymphoproliferative diseases in human; (E) Foot-and-
enfuvirtide (target gp41), raltegravir (integrase inhibitor) etc. Empha-
Mouth Disease Virus (FMDV) causes blisters in mouth and feet of
sizing on combinatorial therapy World Health Organization (WHO)
human and some hoofed animals; (F) Newcastle Disease Virus (NDV)
has recommended HAART for the better management of this fatal
affecting avian species and transmissible to human through poultry
disease.
birds (Swayne and King, 2003). A little information of those viruses
are given below:
3.2. HSV

3.1. HIV Herpes Simplex Virus of Herpes viridae family consists of double-
stranded linear DNA genome wrapped with lipid bilayer envelope. The
Human Immunodeficiency Virus (HIV) is a positive sense, single- outer envelope is attached with the capsid by means of a tegument.
stranded, enveloped, RNA virus belongs to the Retroviridae family. It Entry of HSV into the host cell involves binding of two viral envelope
causes AIDS by attacking immune system of the human body. Gradual glycoproteins called gC and gB with the heparin sulphate receptor of
disruption of immunological balance of human body is initiated through host cellular surface. Next, another glycoprotein gD binds specifically
the killing of immune cells by HIV and this favors an increase of viral to at least one of the three known receptors viz., HVEM, nectin-1 and
load in blood. HIV infection is usually asymptomatic until it progresses heparin sulphate. After binding, gD changes its conformation and inter-
to AIDS. AIDS symptoms include weight loss, fever, sore throat, fatigue, acts with gH and gL to form a complex. This interaction may result in
nausea, diarrhea, vomiting, shortness of breath, severe headache, joint hemifusion state and creation of entry pore takes place. Transcription
pain, chronic cough etc. Severe weakening of immune system makes of HSV genes is catalyzed by RNA polymerase II of host cell. Early gene
the body susceptible for other recurrent infection. If HIV is left un- expression of virus allows the synthesis of enzymes involved in DNA
treated, even a minor infection may be fatal as the body is unable to replication and the production of glycoproteins. Late gene expression
fight off this. About 36.9 million people were living with HIV infection of virus occurs last to encode proteins required for virion particle forma-
in 2017 and Swaziland was marked as most highly affected country tion (Thellman and Triezenberg, 2017). These events are schematically
(Joint United Nations and Programme on HIV/AIDS, 2018). On account presented in Fig. 2.
of the introduction of “Highly Active Antiretroviral Therapy” (HAART) HSV may persist in a quiescent but persistent form, mainly in neural
medical professionals were able to witness a notable drop in AIDS re- ganglia. The rate of infection with HSV (1&2) is around 90%, worldwide.
lated deaths (Chesney, 2003). However, majority of the people is unable More than 3.7 billion people under the age of 50 years are infected with
to access this prolonged therapeutic approach because of high expense HSV-1 according to global estimate of WHO. In USA 22% of adults are
and intolerable side effects. noted to be HSV2-positive and in Europe the figure is around 15%

Surface Cellular
glycoprotein receptor
Viral DNA
Interaction
Integration of viral
DNA into host DNA

HIV
Transcription

Processing
Viral transcript
Nucleus

Host cell Viral proteins

Release of virus

Fig. 1. Infection mechanisms of different viruses against which Moringa oleifera and derived compounds showed promising antiviral activities. HIV infection mechanism.
 D. Biswas et al. / South African Journal of Botany 129 (2020) 272–282 275

Adsorption Membrane
fusion
Penetration
HSV

Tegument
Nucleus enters into cell

Replication
Genome
uncoating

Viral release
Assembly

Host cell

Fig. 2. Infection mechanisms of different viruses against which Moringa oleifera and derived compounds showed promising antiviral activities. HSV infection mechanism.

(Gottlieb and Deal, 2017). Acyclovir, valacyclovir, famicyclovir etc. are the endocytosis mediated by clathrin or caveolin-1. Release of nucleo-
commonly used as the medication for HSV infection. capsid into the host cytoplasm takes place following endocytosis. For
the multiplication of virus, its genomic DNA has to be transferred to
3.3. HBV the host cell nucleus. Thereafter, fully double-stranded DNA from par-
tially double-stranded viral DNA is formed by the host DNA polymerase
Hepatitis B Virus, a double-stranded DNA virus, classified under and subsequently it is transformed into covalently closed circular DNA
Hepadnaviridae, is one of the non-retroviral agent which uses reverse (ccc DNA) which serves as a template for the transcription of four
transcription as a part of its replication process. HBV initially binds to viral mRNAs. The largest mRNA is used to make new genome copies,
heparin sulphate proteoglycan of host cell surface and enters through capsid core protein and viral RNA-dependent-DNA-polymerase. Those

HBV
Receptors
Core assembly and
RNA packaging V
Viral release
Reverse transcription
Viral entry

Translation (-) strand DNA

Nucleus Maturation

(+) RNA progenome (+) strand DNA

Short transcripts
Viral surface proteins
cccDNA Transcription

Translation
RNA Pol II

Hepatocyte

Fig. 3. Infection mechanisms of different viruses against which Moringa oleifera and derived compounds showed promising antiviral activities. HBV infection mechanism.
276 D. Biswas et al. / South African Journal of Botany 129 (2020) 272–282

four viral transcripts undergo additional processing to form progeny vi- 3.5. FMDV
rions (Schädler and Hildt, 2009). A diagrammatic presentation is given
in Fig. 3. Foot-and-mouth disease virus or Aphthovirus of Picornaviridae fam-
Existing antiviral drugs like entecavir, tenofovir, lamivudine, ily possesses single-stranded positive encoding RNA genome without
adefovir, telbivudine etc. can help to fight with that virus and slow envelop. Binding of virus to host cellular receptor triggers a folding-in
down its ability to damage liver. About 70–90% of the population be- of the cell membrane. After the virion entrance, genome uncoating
comes HBV-infected before the age of 40 years and 8–20% people are takes place and replication occurs. Next, translation occurs through a
HBV carrier. Highly HBV affected areas include SE Asia, Pacific Basin, cap-independent mechanism by IRES (Internal Ribosomal Entry Site) el-
Amazon Basin, part of Middle East, the central Asian Republics and ement. Viral proteases inhibit the synthesis of normal cellular protein
some countries in eastern Europe (WHO, 2002). and viral proteins interact with different components of the cell. The in-
fected cells become damaged by producing large quantities of viral RNA
3.4. EBV and capsid proteins which are prerequisite for the new virus assembly.
This virus occurs in seven major serotypes viz., O, A, C, SAT-1, SAT-2,
Epstein Barr Virus which was formerly known as Human gamma SAT-3, Asia-1 among which O is most common (Gao et al., 2016).
herpes virus 4, is one of the life-threatening virus of Herpesviridae Major events are depicted in Fig. 5.
family, causes infectious mononucleosis, several lymphomas and some There is no specific treatment available for this disease. The disease
non-lymphoid malignancies. Genome of this enveloped viral particle symptoms are not so severe, only blisters with mild flu occurs. Common
consists of DNA double helix. EBV infects different types of cells includ- analgesics and antipyretics are often given to relieve sufferings.
ing B cells and epithelial cells. Processes of entering into these two types
of cells are different from each other. B cell entry is initiated with the
binding of viral glycoprotein gp350 to host cellular receptor CD21 (or 3.6. NDV
CR2). Then viral glycoprotein gp42 interacts with MHC II of host cell
and this triggers the fusion of viral envelope with host cellular mem- Newcastle Disease Virus or Avian avulavirus 1 falls under Paramixov-
brane allowing the viral entry into B cell. Another cellular factor CD35 iridae family, attacks mainly avian species and affects severely the poul-
(or CR1) provides a route for EBV entry into the CD21 negative cells, in- try industries. Generally, this infection consists of signs like depression,
cluding immature B cells. EBV infection downregulates CD35 expression diarrhea, prostration, edema, paralysis, torticollis and respiratory disor-
of host cells. Interaction between viral protein BMRF-2 and cellular β1 der in birds. NDV is spreadable primarily through direct contact be-
integrins mediates entry of EBV into the epithelial cells. Afterwards, tween healthy birds and the bodily discharges of infected birds.
viral protein gH/gL interacts with cellular αvβ6/αvβ8 integrins. Trigger- Exposure of human beings to the infected birds (e.g. from poultry) can
ing the fusion of the viral envelope with the epithelial cell membrane cause mild conjunctivitis and influenza-like symptoms. No treatment
that interaction allows epithelial-cell entry of EBV. Lytic cycle involves is available for NDV infection but prophylactic vaccines can reduce the
viral DNA polymerase for replication which results the production of in- likelihood of outbreaks. Antibiotics may assist to control secondary
fectious virion particles. Opposed to this, in latency circular EBV DNA re- infection.
mains in the cell nucleus as an episome and is copied through cellular NDV strains can be categorized into three types namely velogenic
DNA polymerase (Csween and Crawford, 2003). A comprehensive dia- (highly virulent), mesogenic (intermediate virulence) and lentogenic
gram is included here (Fig. 4). (nonvirulent). Velogenic strains are responsible for severe nervous
Infants become susceptible to EBV infection as soon as maternal an- and respiratory signs, spread rapidly and cause upto 90% mortality.
tibody protection disappears. However, in childhood this infection is Mesogenic strains affect production and quality of eggs and results
more or less asymptomatic. During adolescence, EBV causes infectious about 10% mortality. Lentogenic strains produce mild signs of infection
mononucleosis by 35–50%. Using chemotherapeutic agents like with negligible mortality(Swayne and King, 2003). A diagram of the
gancyclovir, cis-platinum, 5-fluorouracil, taxol etc. is a regular practice life-cycle of this enveloped, negative sense, single-stranded RNA virus
to lessen the deadly effects of the functional infection of EBV. is outlined in Fig. 6.

EBV infected plasma

EBV
cell
Viral replication

Epithelium

Viral
replication EBV infected memory B
cell

EBV infection
of naive B cell

EBV infected germinal

centre B cell

EBV infected blast

Cytotoxic T cell

Fig. 4. Infection mechanisms of different viruses against which Moringa oleifera and derived compounds showed promising antiviral activities. EBV infection mechanism.
 D. Biswas et al. / South African Journal of Botany 129 (2020) 272–282 277

Integrin
FMDV
receptor

Host cell membrane inward folding

(+ve)RNA synthesis

dsRNA intermediate

(-ve)RNA synthesis
Viral entry

Genome uncoating

Encapsidation

Translation Nucleus
Pentamer

Non-structural
proteins Processing
Ribosome

Structural
proteins

Fig. 5. Infection mechanisms of different viruses against which Moringa oleifera and derived compounds showed promising antiviral activities. FMDV infection mechanism.

4. Antiviral potentiality of M. oleifera field of drug development approaches. Moringa oleifera is one of the
important medicinal plant possessing an indicative number of biochem-
Efforts to develop alternative antiviral therapeutic agents with sig- ical compounds according to GC–MS analysis (Aja et al., 2014).
nificant mode of action, acceptable toxicity and less resistant profile Compounds like L-ascorbic acid, oleic acid, 9-octadecenoic acid, phytol,
have generated interest to find out potential drug leads from bioactive N-(-1-methylethyllidene) benzene ethanamine, 3, 4-epoxy-ethanone,
natural compounds of plant origin. Unfortunately, it is hard to use tradi- 4-hydroxy-4-methyl-2-pentane, 3-ethyl-2,4-dimethyl-pentane, 1-
tional healers universally to the infectious diseases due to paucity of in- hexadecanol, octadecamethyl–cyclononasiloxane, hexadecanoic acid,
formation. It necessitates enrichment of indigenous knowledge of 3,5-bis (1,1-dimethylethyl)-phenol etc. found in this plant extract
medicinal plants based on ethnopharmacological data required in the should be considered for proper screening of antiviral potential,

Viral entry

Replication

NDV
(-) Genome (+) Antigenome

Transcription Replication
Transcription
Cap AAA
Cap AAA (-) Genome
Cap AAA
Translation
Capsid proteins
Matrix protein

Attachment proteins
Nucleus

Budding and
viral release
Host cell

Fig. 6. Infection mechanisms of different viruses against which Moringa oleifera and derived compounds showed promising antiviral activities. NDV infection mechanism.
278 D. Biswas et al. / South African Journal of Botany 129 (2020) 272–282

separately. It is noteworthy that the plant M. oleifera (Moringaceae) phytotherapy (Sebit et al., 2000). The informative data obtained from
showed remarkable inhibitory activity specifically against six different their report have supported the role of phytotherapy in improving the
viruses as reported by several authors. Relevant information obtained quality of life of HIV-I-infected patients, significantly. In silico study
from their study are presented in Table 3 which summarizes the inhib- based on ligand–receptor binding i.e. molecular docking is an innova-
itory activity of M. oleifera extracts and compounds against six different tive approach to determine the interaction between drug leads and
viruses with notes on their mode of action. Fig. 7 represents the chem- viral proteins based on dock pose analysis prior to in vitro experimenta-
ical structures of the antiviral compounds derived from the plant. tion. It may be utilized as a guideline through the view of reducing un-
necessary expenditure in random “wet lab” screening methods. An
attempt has been made by Sangar et al. (2015) for detecting the role
4.1. HIV inhibitory activity of M. oleifera in HIV treatment using CXCR4 as a target receptor. Docking
was done using Autodock 4 software for the analysis of 18 selected
Being rich in vitamin and other nutrients including β-carotene, po- phyto-constituents of this plant (Sangar et al., 2015). On the basis of
tassium, calcium, magnesium, sulfur and phosphorus with a good safety docking score analysis ellagic acid and aurantiamide acetate may be
profile,the extract of M. oleifera plant is generally advocated to HIV pa- considered as promising candidates against CXCR4 receptor among 18
tients along with anti-retroviral therapy as a nutritional supplement test compounds. Further extensive study should be continued to
and immune booster. Thirty-three HIV patients were screened after explore unique anti-HIV activity of this plant in vitro and in vivo and po-
supplementation of M. oleifera leaf powder along with the medication tential bioactive lead molecules.
of nevirapin, a commonly used antiretroviral drug (Monera et al.,
2012). Since the safety profile of nevirapine is not affected by Moringa
oleifera when co-administered to HIV-infected patients, this well-toler- 4.2. HSV inhibitory activity
ated combinatorial therapy may be applied, frequently. The inhibitory
activity of three different extracts of M. oleifera on lentiviral vector infec- Drumstick (M. oleifera), as a wholesome for HSV infected individuals
tivity was studied in HeLa cell lines in vitro (Nworu et al., 2015). Here, is included in primary healthcare system since a long ago. Researchers
each of the extracts were active against HIV lentiviral vector and have observed the direct effects of this plant on HSV strains through
inhibited early events of viral replication in certain concentration- several in vitro experiments. Aqueous extract of M. oleifera inhibited
dependent manner. Aqueous extract, methanolic extract and petroleum HSV type 1 & type 2 by 43.2% and 21.4%, separately at the concentration
ether extract of M. oleifera leaf have shown EC50 values of 7.17, 7.72 and of 200 μg ml−1(Rosmarinus et al., 2017). Compounds like dibutyl
7.59 μg ml−1, respectively. Bioactivities may be attributed to the con- phthalate, 4-dodecanol, hentriacontane, squalene, tetracontane-1,40-
tents of saponins, alkaloids, glycosides, tannins, carbohydrates, flavo- diol, alpha tocopherol, beta amyrin etc. present in plant extract may
noids, resins, acidic compounds and proteins present in the leaf be responsible for mediating that promising antiviral potentiality, like-
extract. Tshingani et al. (2017) have selected 60 HIV-infected patients wise. Crude ethanolic extract of M. oleifera leaves attenuated the activity
at the stage of clinical trial II for their study. Among them 30 randomly of HSV-1, specifically with EC50 value of 100 ± 5.3 μg ml−1which was
chosen patients were given 30 g of M. oleifera leaf powder (an amount of found in an authentic document (Li et al., 2018). Aqueous extract of
10 g thrice) daily over six months and the rests were kept as control M. oleifera leaves activated cellular immunity in HSV-1 infected mice
providing nutritional counseling only. After this six months follow-up, by reducingtheviral load and related skin lesion as reported by
the patients consuming M. oleifera leaf powder exhibited a significant Yoshida et al. (2016). Their HPLC analysis have confirmed the presence
increase in body mass index and amount of albumin in blood as com- of myricetin, apigenin and chrysin as flavonoid constituents having the
pared with the control ones (Tshingani et al., 2017). Comparative probable ability to hinder viral growth (Yoshida et al., 2016). According
study of the steady-state pharmacokinetics between two synthetic to the report of Pramyothin et al. (2003) it is evident that water and
drugs, nevirapin and efavirenz was done before and after supplementa- ethanolic extract of M. oleifera have shown significant prophylactic ac-
tion with M. oleifera leaf powder in HIV positive people. Here, 19 HIV- tivity by inhibiting more than 50% of plaque formation of Herpes Sim-
affected people were studied thoroughly to examine the impact of plex Virus type 1 (HSV-1) at a measurable dose of 100 μg ml−1

Table 3
Summary of the inhibitory activity of Moringa oleifera against six different viruses.

Name Types Plant Solvent/chemicals compounds Mode of action EC50 CC50 Reference
of virus of strain part used (μg ml−1) (μg ml−1)

HIV 1 Leaves Water, Methanol, Petroleum ether Inhibited viral 7.17, 7.72, 41.58, E et al., (2015), Sangar et al.
replication 7.59 38.88, (2015)
Ellagic acid, aurantiamide acetate Taergeted CXCR4 32.33
HSV 1&2 Leaves Water, Ethanol Activated cellular 100, 100 ± ≥200 (Rosmarinus et al. (2017), Li et al.
aurantimide acetate, benzyl isothiocyanate, immunity; Hindered 5.3, 74.8 ± (2018), Pramyothin et al. (2003),
chlorogenic acid, benzyl glucosinolate, quercetin, viral growth 4.7 Goswami et al. (2016), Yoshida
moringinin, niazimicin, niaziminin, apigenin, chrysin, et al. (2016)
myricetin, pterygospermin, dibutyl phthalate,
squalene, alpha- tocopherol, beta amyrin
HBV C&H Leaves Water, 80% hydroalcoholic solvent, 50 mM Tris–HCl Decreased HBsAg, ≈45–50 ≤500 Feustel et al. (2017), Waiyaput
buffer(pH 7.5) CTGF, TGF-β1, IL-6, et al. (2012)
cccDNA; Increased
CAT expression
EBV – Leaves, Ethanol, Methanol Showed inhibitory 32.7, 35.3, ≥100 Murakami et al. (1998), Maoka
Seeds 4-(α-L-rhamnosyloxy)benzyl isothiocyanate, activity against 27.9, 13.0 et al. (1999)
niazimicin, β-sitosterol-3-O-β-D-glucopyranoside, EBV-EA activation
niaziminin
FMDV – Leaves Chloroform, Ethanol Targeted ≤50 ≥100 Younus et al. (2016)
protein/enzymes of
viral replication cycle
NDV – Leaves Methanol Immune booster Not Not Okwor et al. (2013), Eze et al.
determined determined (2014)
 D. Biswas et al. / South African Journal of Botany 129 (2020) 272–282 279

Ellagic acid Aurantiamide acetate Benzyl glucosinolate β-amyrin

Benzyl isothiocyanate Dibutyl phthalate Pterygospermin Apigenin

Chrysin Myricetin Quercetin Chlorogenic acid

Fig. 7. Bioactive compounds obtained from Moringa oleifera.

(Pramyothin et al., 2003). Goswami et al. (2016) reported that the (2012) prepared two types of M. oleifera extracts using two different
methanolic extract of M. oleifera leaves exhibited discernible inhibitory solvents viz., 80% hydroalcoholic solvent and a 50 mM Tris–HCl buffer
activity against HSV-1 with EC50 value of 74.8 ± 4.7 μg ml−1at non- (pH 7.5) and evaluated HBV inhibitory effect of the respective plant in
cytotoxic concentration (Goswami et al., 2016). They have isolated sev- COS-7 and HepG2 cell lines through several laboratory experiments.
eral phytochemicals like aurantimide acetate, benzyl isothiocyanate, Hydroalcoholic extract of M. oleifera drastically decreased the level of
chlorogenic acid, benzyl glucosinolate, quercetin, moringinin, niazim- cccDNA in transiently transfected HepG2 cells. Tris–HCl buffer
icin, niaziminin, pterygospermin etc. for the elucidation of the bioactive (pH 7.5) extracts of M. oleifera also showed anti-HBV activity with a
potency of that plant in future. mild cytotoxicity (Waiyaput et al., 2012). These promising results are
needed to be analyzed further along with isolation of phytochemicals
4.3. HBV inhibitory activity and molecular identification of viral targets, meticulously.

This hepatotropic virus is culpable for several liver functions impair- 4.4. EBV inhibitory activity
ment and eventual development of hepatocellular carcinoma. Interna-
tional guidelines have stated about the long term administration of Once the establishment of successful infection of EBV, it takes 4–
antiviral drugs to reduce the severity of infection and histological im- 6 weeks to show up symptoms including fatigue, fever, lack of appetite,
provement. Normalization of liver function is not achieved very fre- skin rash, sore throat, swollen glands in the neck, weakness and sore
quently through the conventional chemotherapy. Intended to hunt muscle, commonly. Transmission of EBV mainly occurs through inti-
alternative therapeutic strategy scientists are interested to employ mate saliva contact in infectious stage. In addition, passing through
plant source at present. Feustel et al. (2017) examined the effect of M. the placental barrier this virus may infect fetus in infected pregnant
oleifera aqueous leaf extract in transfected Huh7 cells expressing C and woman when reactivated during its post latency stage. In severe cases
H genotypes of HBV strains. The HBsAg secretion in the supernatant of no antiviral drugs or vaccines work effectively in stoppage of viral
transfected Huh7 cells with genotypes C and H of HBV was decreased build out within human body. Attempt to develop functional remedy
independently with M. oleifera treatment. CTGF and TGF-β1gene ex- have generated interest within researchers to study the natural prod-
pression were decreased also in comparison with the control ones. ucts in this regard. Maoka et al. (1999) isolated seven biochemical com-
Transfection of those cells with both HBV genotypes strongly decreased pounds from ethanolic extract of M. oleifera seeds. These are the
CAT expression, which was restored with M. oleifera treatment, conspic- followings: (i) O-ethyl-4-(α-L-rhamnosyloxy) benzyl carbamate, (ii)
uously. Moringa oleifera treatment reduced the IFNβ1 gene expression 4-(α-L-rhamnosyloxy) benzyl isothiocyanate, (iii) niazimicin, (iv)
slightly higher in genotype H than that of genotype C. After treating niazirin, (v) β-sitosterol, (vi) glycerol-1-(9-octadenoate), (vii) 3-O-
with M. oleifera, IL-6 showed a tendency to decrease in a dose- (6′-O-oleoyl-β-D-glucopyranosyl)-β-sitosterol and (viii)β-sitosterol-3-
dependent manner in the supernatant of Huh7-transfected cells with O-β-D-glucopyranoside. All the compounds were tested for their
genotypes C and H, positively (Feustel et al., 2017). Waiyaput et al. inhibitory effects on Epstein–Barr virus-early antigen (EBV-EA)
280 D. Biswas et al. / South African Journal of Botany 129 (2020) 272–282

activation in Raji cells induced by the tumor promoter, 12-O- improved in birds, significantly (Eze et al., 2014). From the above-men-
tetradecanoyl-phorbol-13-acetate (TPA). Each of these showed consid- tioned observations, it can inferred that large scale use of M. oleifera
erable inhibitory activity against EBV-EA activation whereas com- supplement along with vaccination against NDV might be possible
pounds (ii), (iii) and (viii) have given remarkable results with EC50 after in-depth investigational study.
values of 32.7, 35.3, 27.9 μg ml−1, respectively without exhibiting any
significant cytotoxicity (Maoka et al., 1999). Murakami et al. (1998) iso- 5. Discussion
lated three compounds viz., niazimicin, niaziminin, 4-(4′-O-acetyl-α-L-
rhamnosyloxy) benzyl isothiocyanate from the metanolic extract of M. A number of bioactive compounds obtained from M. oleifera plant
oleifera leaves. Among these onlyniaziminin (a thiocarbamate) showed are waiting to be evaluated for potential antiviral activities and for the
significant inhibition against EBV activation in Raji cells. They have discovery of the mode of action, accordingly. Massive experimental
stated that only one acetyl group should be present compulsorily at studies are needed to be carried out for genuine utilization of those phy-
the oxygen of the 4′-position without the presence of any other acetyl tochemicals. Those compounds should be evaluated against other simi-
group to the remaining hydroxyl groups of the sugar moiety of this com- lar type of viruses to inspect their diverse activities. Moreover, efficacy
pound (Murakami et al., 1998). Detailed investigation of the activities of of those compounds in vivo may not be matched with the procured out-
prospective lead molecules is needed for the proper utilization of the come of in vitro experimentation because of body's own metabolism
medicinal value of M. oleifera regarding various target inhibition of system which is totally different from laboratory condition. Frequent
this deadly virus. animal model based studies following proper guidelines are necessary
as per the requirement for clinical trials of prospective natural products.
4.5. FMDV inhibitory activity No clinical study has been recorded in order to authenticate the prom-
ising antiviral efficacy of the plant. The only clinical study using M.
Spreading of highly contagious foot mouth disease occurs through oleifera was performed to evaluate its anti-asthmatic activity which re-
infected individuals plus aerosol transmission within human and vealed its safe and efficacious applications on human samples (Agrawal
hoofed livestock. Most of the countries are now trying to invent pro- and Mehta, 2008). However, the detailed clinical and experimental tri-
gressive control pathway for this disease outbreak cost effectively. als are needed to investigate its underlying mode of action and thera-
They are interested to utilize effectual bioactive plant products in lieu peutic ability especially as an antiviral agent. Moreover, no structure
of applying hazardous chemotherapeutic strategies. Younus et al. activity relationship studies have been carried out to elucidate the role
(2016) carried out MTT colorimertic assay to evaluate antiviral and cy- of M. oleifera phytochemicals as antiviral agents. More clinical studies
totoxic activity of chloroformic extract of M. oleifera leaves in are necessary to find out the necessity and feasibility to generate syn-
diminishing FMDV infection in BHK-21 cell line. Concentration of the re- thetic antiviral drugs using Moringa derived natural compounds as tem-
spective plant extract ranges from 1 to 50 μg ml−1 have indicated signif- plate. After authentic validation of experimental studies it might be
icant activity in comparison with the rests. Observing this, the authors possible to use the plant constituents universally in treating incurable
have recommended for future studies aiming to elucidate the mode of viral diseases including the de novo development of promising drugs.
action of this inexpensive and easily available plant resource (Younus According to the report of World Health Organization (WHO), the
et al., 2016). Imran et al. (2016) prepared ethanolic extract of M. oleifera use of natural bioactive compounds throughout the world now exceeds
plant and diluted with M-199 cell culture media and then performed by two to three times higher than that of conventional drug candidates
MTT colorimetric assay using BHK-29 cell line. The plant extract showed (WHO, 2013). The great demand for plant-based medicinal compounds
considerable antiviral activity against FMDV at concentration ranges of has been developed because of their wide biological activities, high
50–300 μg ml−1and revealed cytotoxicity at higher concentration safety and lesser cost. Their global market currently stands at over
(100 μg ml−1) (Imran et al., 2016). Investigational research should be $ 60 billion annually (Gunjan et al., 2015). Lack of ethnomedicinal infor-
continued to develop efficient, less resistant, low cost and easily avail- mation, insufficient knowledge of plant metabolites, problem of
able bioactive product against FMDV. obtaining large-scale supply of promising plant-derived compounds
and lack of necessary funding have made great challenges to face.
4.6. NDV inhibitory activity Proper survey of botanically rich areas, improvement of tissue culture
methods for growing medicinally important plants and involvement
In 1926, the first outbreaks of Newcastle disease occurred in of much more funding agencies in multidisciplinary analytical research
chickens in Indonesia and England and NDV was recognized as the eti- are essential regarding these issues to address the necessity of prospec-
ologic agent (Swayne and King, 2003). It is a serious threat for poultry tive bioactive plant compounds in drug development approaches.
industry due to high mortality rate. It is essential to block the spreading
of this disease as early as possible to reduce economic loss. Being a mul- 6. Conclusion
tipurpose medicinal plant, M. oleifera have drawn attention of re-
searchers in arresting the epidemic of Newcastle disease. Okwor et al. Medicinal properties of M. oleifera plant possess a long history of
(2013) investigated the effects of crude methanolic extract of M. oleifera uses because of better tolerance, low cost and easy availability in coun-
in chickens experimentally challenged with velogenic Newcastle Dis- tries like India which have good agricultural condition and rich regional
ease Virus. They randomly divided experimental birds into four equal distribution of that plant. Now, the plant has become an indispensable
groups of 30 chicks where groups I and II were treated orally with part of public healthcare throughout the world. Various survey reports
200 mg kg−1 body weight of the plant extract daily for two weeks, have highlighted on its widespread uses. However, reckless utilization
groups II and III were vaccinated and group IV was kept untreated. of this plant resource may threaten its sustainability. It is necessary to
Moringa oleifera extract increased Newcastle Disease Haemaagglutin- preserve this important plant as soon as possible for further uses. Clonal
ation Inhibition titer as well as the total and differential leukocyte propagation may be a useful tool for the regeneration of required plant
counts in the treated and unvaccinated group I birds much more than parts possessing expected antiviral activities. Abuses like grazing, defor-
those of treated and vaccinated group II. Henceforth, this plant extract estation and other destructive human activities in the respective area
may be recommended as an immune-booster in non-vaccinated birds should be stopped through making laws with respective rules and rec-
to fight against the lethal infection (Okwor et al., 2013). Comparative ommendations. To avail medicinal benefits from this enriched plant re-
study was performed by using the plant extract plus vaccination and source, research activities should be encouraged by regional, national
Vacci-Boost supplementation with vaccination, separately in different and international funding and other necessary supportive activities.
group of chicken birds. In both ambiences immune response was Besides, rigorous pre-clinical and clinical trials and elucidation of
 D. Biswas et al. / South African Journal of Botany 129 (2020) 272–282 281

structure–activity relationships of the compounds obtained from the Gopalakrishnan, L., Doriya, K., Kumar, D.S., 2016. Moringa oleifera: a review on nutritive
importance and its medicinal application. Food Sci. Human Wellness 5, 49–56.
plant are needed to assess the druggability of the natural templates Goswami, D., Mukherjee, P.K., Kar, A., Ojha, D., Roy, S., Chattopadhyay, D., 2016. Screening
and also to better understand the underlying mechanism of action of of ethnomedicinal plants of diverse culture for antiviral potentials. Indian J. Tradit.
antiviral properties of this potent ethnomedicinal plant. Knowl. 15, 474–481.
Gottlieb, S., Deal, C., 2017. Herpes Simplex Virus (HSV) Vaccine Development Update.
WHO.
Gunjan, M., Naing, T.W., Saini, R.S., Ahmad, A., Naidu, J.R., Kumar, I., 2015. Marketing
Declaration of Competing Interest trends & future prospects of herbal medicine in the treatment of various disease.
World J. Pharm. Res 4, 132–155. https://doi.org/10.20959/wjpr20168-6435.
Imran, I., Altaf, I., Ashraf, M., Javeed, A., Munir, N., Bashir, R., 2016. In Vitro evaluation of
There is no conflict of interest. antiviral activity of leaf extracts of Azadirachta indica, Moringa oleifera, and Morus
alba against the foot and mouth disease virus on BHK-21 cell line. Sci. Asia 42,
Acknowledgements 392–396.
Joint United Nations, Programme on HIV/AIDS, 2018. UNAIDS data 2018. p. 376 https://
doi.org/978-92-9173-945-5.
The corresponding author acknowledges “Faculty Research and Kamagaju, L., Bizuru, E., Minani, V., Morandini, R., Stévigny, C., Ghanem, G., Duez, P., 2013.
Professional Development Fund” (FRPDF) from Govt. of West Bengal An ethnobotanical survey of medicinal plants used in Rwanda for voluntary depig-
mentation. J. Ethnopharmacol. 150, 708–717.
(2012-2018), and DBT-BUILDER from Department of Biotechnology, Khan, S., Balick, M.J., 2001. Therapeutic plants of Ayurveda: a review of selected clinical
Govt. of India (BT/PR-11357/INF/22/197/2014, Dt 28.03.2014). and other studies for 166 species. J. Altern. Complement. Med. 7, 405–515.
Kirchhoff, F., 2013. HIV life cycle: overview. Encycl. AIDS, 1–9 https://doi.org/10.1007/
978-1-4614-9610-6_60-1.
References Kuben, K.N., Roger, M.C., 2016. Review on herbal remedies used by the 1860 South African
Indian settlers. Afr. J. Biotechnol. 10, 8533–8538. https://doi.org/10.5897/ajb11.003.
Abd-Rabou, A.A., Abdalla, A.M., Ali, N.A., Zoheir, K.M.A., 2017. Moringa oleifera root in-
Lamorde, M., Tabuti, J.R., Obua, C., Kukunda-Byobona, C., Lanyero, H., Byakika-Kibwika, P.,
duces cancer apoptosis more effectively than leave nanocomposites and its free coun-
Bbosa, G.S., Lubega, A., Ogwal-Okeng, J., Ryan, M., Waako, P.J., 2010. Medicinal plants
terpart. Asian Pac. J. Cancer Prev 18, 2141–2149. https://doi.org/10.22034/
used by traditional medicine practitioners for the treatment of HIV/AIDS and related
APJCP.2017.18.8.2141.
conditions in Uganda. J. Ethnopharmacol. 130, 43–53.
Abe, R., Ohtani, K., 2013. An ethnobotanical study of medicinal plants and traditional ther-
Li, W., Wang, X.H., Luo, Z., Liu, L.F., Yan, C., Yan, C.Y., Chen, G.D., Gao, H., Duan, W.J.,
apies on Batan Island, the Philippines. J. Ethnopharmacol. 145, 554–565.
Kurihara, H., Li, Y.F., He, R.R., 2018. Traditional chinese medicine as a potential source
Abraham, I., Andrew, N., Godwin, O., 2014. Antibacterial effect of Moringa oleifera extracts
for hsv-1 therapy by acting on virus or the susceptibility of host. Int. J. Mol. Sci. 19,
on bacteria associated with urinary tract infection. Int. J. Res. 1, 1308–1316.
1–23. https://doi.org/10.3390/ijms19103266.
Agoyi, E.E., Assogbadjo, A.E., Gouwakinnou, G., Okou, F.A., Sinsin, B., 2014. Ethnobotanical
Mann, A., Amupitan, J.O., Oyewale, A.O., Okogun, J.I., Ibrahim, K., 2007. An Ethnobotanical
assessment of Moringa oleifera Lam. in Southern Benin (West Africa). Ethnobot. Res.
survey of indigenous flora for treating tuberculosis and other respiratory diseases in
Appl. 12, 551–560.
Niger State, Nigeria. J. Phytomed. Therapeut. 12, 1–21.
Agrawal, B., Mehta, A., 2008. Antiasthmatic activity of Moringa oleifera Lam: a clinical
Maoka, T., Kozuka, M., Sakurai, H., Nishino, H., Fujiwara, Y., Guevara, A.P., Ito, Y.,
study. Ind. J. Pharmacol. 40, 28.
Hashimoto, K., Vargas, C., Tokuda, H., 1999. An antitumor promoter from Moringa
Aja, P.M., Nwachukwu, N., Ibiam, U.A., Igwenyi, I.O., Offor, C.E., Orji, U.O., 2014. Chemical
oleifera Lam. Mutat. Res. Toxicol. Environ. Mutagen. 440, 181–188. https://doi.org/
constituents of Moringa oleifera leaves and seeds from Abakaliki, Nigeria. Am.
10.1016/s1383-5718(99)00025-x.
J. Phytomed. Clin. Ther. 2, 310–321.
Maroyi, A., 2011. An ethnobotanical survey of medicinal plants used by the people in
Al-Shahrani, H., Khan, A.Q., Albalawi, S.M., Islam, M., Athar, M.T., Al-Asmari, A.K., 2015.
Nhema communal area, Zimbabwe. J. Ethnopharmacol 136, 347–354.
Moringa oleifera as an anti-Cancer agent against breast and colorectal cancer cell
Matic, I., Guidi, A., Kenzo, M., Mattei, M., Galgani, A., 2018. Investigation of medicinal
lines. PLoS One 10, e0135814. https://doi.org/10.1371/journal.pone.0135814.
plants traditionally used as dietary supplements: a review on Moringa oleifera.
Amri, E., Kisangau, D.P., 2012. Ethnomedicinal study of plants used in villages around
J. Public Health Afr. 9, 841.
Kimboza forest reserve in Morogoro, Tanzania. J. Ethnobiol. Ethnomed. 8, 1.
Monera, T.G., Maponga, C.C., Christian, N., 2012. Prevalence and patterns of Moringa
Asiimwe, S., Kamatenesi-Mugisha, M., Namutebi, A., Borg-Karlsson, A.-K., Musiimenta, P.,
oleifera use among HIV positive patients in Zimbabwe: a cross-sectional survey.
2013. Ethnobotanical study of nutri-medicinal plants used for the management of
J. Public Health Afr. 3, 6–8. https://doi.org/10.4081/jphia.2012.e6.
HIV/AIDS opportunistic ailments among the local communities of western Uganda.
Morimitsu, Y., Hayashi, K., Nakagama, Y., Horio, F., Uchida, K., Osawa, T., 2000. Antiplatelet
J. Ethnopharmacol. 150, 639–648.
and anticancer isothiocyanates in Japanese horseradish, wasabi. Biofactors 13,
Ayyanar, M., Ignacimuthu, S., 2011. Ethnobotanical survey of medicinal plants commonly
271–276.
used by Kanitribals in Tirunelveli hills of Western Ghats, India. J. Ethnopharmacol.
Murakami, A., Kitazono, Y., Jiwajinda, S., Koshimizu, K., Ohigashi, H., 1998. Niaziminin, a
134, 851–864.
thiocarbamate from the leaves of Moringa oleifera, holds a strict structural require-
Cáceres, A., Freire, V., Girón, L.M., Avilés, O., Pacheco, G., 1991. Moringa oleifera
ment for inhibition of tumor. Planta Med. 64, 319–323.
(Moringaceae): ethnobotanical studies in Guatemala. Eco. Bot. 45, 522–523.
Mustapha, A.A., 2014. Ethnobotanical field survey of medicinal plants used by traditional
Chesney, M., 2003. Adherence to HAART regimens. AIDS Patient Care STDS 17, 169–177.
medicine practitioners to manage HIV/AIDS opportunistic infections and their pro-
https://doi.org/10.1089/108729103321619773.
phylaxis in Keffi Metropolis, Nigeria. Asian J. Plant Sci. Res. 4, 7–14.
Chinsembu, K.C., Hedimbi, M., 2010. An ethnobotanical survey of plants used to manage
Noumi, E., Manga, P.N., 2011. Traditional medicines for HIV/AIDS and opportunistic infec-
HIV/AIDS opportunistic infections in Katima Mulilo, Caprivi region, Namibia.
tions in north-West Cameroon: case of skin infections. Am. J. Trop. Med. Hyg. 1,
J. Ethnobiol. Ethnomed. 6, 25.
44–64.
Csween, K.F., Crawford, D.Hm., 2003. EBV life cycle. Lancet Infect. Dis. 3, 131–140.
Nworu, E.L., Esimone, C.O., Ezeifeka, C.S., Okoye, G.O., 2015. Extracts of Moringa oleifera
Eze, D.C., Okwor, E.C., Ehirim, C.H., Ibu, J.O., Shoyinka, S.V.O., 2014. Comparative evalua-
Lam. showing inhibitory activity against early steps in the infectivity of HIV-1
tion of Moringa oleifera and vacci-boost immuno- modulators in chickens experimen-
lentiviral particles in a viral vector-based screening. Afr. J. Biotechnol. 12,
tally infected with Newcastle Disease Virus (Kudu 113 Strain). South Asian J. Exp.
4866–4873. https://doi.org/10.5897/ajb2013.12343.
Biol. 4, 42–47.
Ohemu, T.L., Agunu, A., Olotu, P.N., Ajima, U., Dafam, D.G., Azila, J.J., 2014. Ethnobotanical
Faizal, A., Razis, A., Ibrahim, M.D., Kntayya, S.B., 2014. Health benefits of Moringa
Survey of Medical Plants Used in the Traditional Treatment of Viral Infections in Jos,
oleifera. Asian Pacific J. Cancer Prev. 15, 8571–8576. https://doi.org/10.7314/
Plateau State, Nigeria.
APJCP.2014.15.20.8571.
Okwor, E.C., Okoye, J.O., Onah, D.N., 2013. Immunologic effects of Moringa oleifera
Farooq, F., Rai, M., Tiwari, A., Khan, A.A., Farooq, S., 2012. Medicinal properties of Moringa
methanolic leaf extract in chickens infected with Newcastle disease virus
oleifera: an overview of promising healer. J. Med. Plant Res. 6, 4368–4374. https://doi.
(kudu 113) strain. Afr. J. Pharm. Pharmacol. 7, 2231–2237. https://doi.org/
org/10.5897/JMPR12.279.
10.5897/AJPP2013.3471.
Feustel, S., Ayón-Pérez, F., Sandoval-Rodriguez, A., Rodríguez-Echevarría, R., Contreras-
Olorunnisola, O.S., Adetutu, A., Balogun, E.A., Afolayan, A.J., 2013. Ethnobotanical survey of
Salinas, H., Armendáriz-Borunda, J., Sánchez-Orozco, L.V., 2017. Protective effects of
medicinal plants used in the treatment of malarial in Ogbomoso, Southwest Nigeria.
Moringa oleifera on HBV genotypes C and H transiently transfected Huh7 cells.
J. Ethnopharmacol. 150, 71–78.
J. Immunol. Res. 2017. https://doi.org/10.1155/2017/6063850.
Paikra, B.K., Dhongade, H.K.J., Gidwani, B., 2017. Phytochemistry and pharmacology of
Flora, S.J., Pachauri, V., 2011. Moringa (Moringa oleifera) seed extract and the
Moringa oleifera Lam. J. Pharmacopuncture. 20, 194–200.
prevention of oxidative stress. Nuts Seeds Health Dis Prevent. Academic Press,
Patel, P., Patel, N., Patel, D., Desai, S., Meshram, D., 2014. Phytochemical analysis and anti-
pp. 775–785.
fungal activity of Moringa oleifera. Int. J. Pharm. Pharm. Sci. 6, 144–147. https://doi.
Ganie, S.A., Zaffer, M., Gulia, S.S., Yadav, S.S., Singh, R., Ganguly, S., 2015. Antifungal effi-
org/10.1016/j.gca.2004.10.019.
cacy of Moringa oleifera Lam. Am. J. Phytomedicine Clin. Ther. 3, 028–033.
Popoola, J.O., Obembe, O.O., 2013. Local knowledge, use pattern and geographical distri-
Gao, Y., Sun, S.Q., Guo, H.C., 2016. Biological function of foot-and-mouth disease virus
bution of Moringa oleifera Lam. (Moringaceae) in Nigeria. J. Ethnopharmacol. 150,
non-structural proteins and non-coding elements. Virol. J. 13, 1–17. https://doi.org/
682–691.
10.1186/s12985-016-0561-z.
Pramyothin, P., Suttisri, R., Lipipun, V., Kurokawa, M., Shiraki, K., Hattori, M.,
Gbadamosi, I.T., 2014. Ethnobotanical survey of plants used for the treatment and man-
Taweechotipatr, P., 2003. Efficacy of Thai medicinal plant extracts against herpes sim-
agement of sexually transmitted infections in Ibadan, Nigeria. Ethnobot. Res. Appl.
plex virus type 1 infection In Vitro and in vivo. Antiviral Res. 60, 175–180. https://doi.
12, 659–669.
org/10.1016/s0166-3542(03)00152-9.
282 D. Biswas et al. / South African Journal of Botany 129 (2020) 272–282

Rahman, M.M., Sheikh, M.M.I., Sharmin, S.A., Islam, M.S., Rahman, M.A., Rahman, M.M., Thellman, N.M., Triezenberg, S.J., 2017. Herpes simplex virus establishment, maintenance,
Alam, M.F., 2009. Antibacterial activity of leaf juice and extracts of Moringa oleifera and reactivation: in vitro modeling of latency. Pathogens 6, 14. https://doi.org/
Lam. against some human pathogenic bacteria. Chiang Mai Univ. J. Nat. Sci. 8, 10.3390/pathogens6030028.
219–228. https://doi.org/10.1111/ajpy.12102. Tshingani, K., Donnen, P., Mukumbi, H., Duez, P., Dramaix-wilmet, M., 2017. Impact of
Rathi, B.S., Bodhankar, S.L., Baheti, A.M., 2006. Evaluation of aqueous leaves extract of Moringa oleifera lam. leaf powder supplementation versus nutritional counseling on
Moringa oleifera Linn for wound healing in albino rats. Indian J. Exp. Biol. 44, 898–901. the body mass index and immune response of HIV patients on antiretroviral therapy:
Rosmarinus, R., Nasr-eldin, M.A., Abdelhamid, A.G., Baraka, D.M., 2017. Antibiofilm and a single-blind randomized control trial. BMC Complement. Altern. Med. 17, 1–13.
antiviral potential of leaf extracts from Moringa oleifera and rosemary (Rosmarinus https://doi.org/10.1186/s12906-017-1920-z.
officinalis Lam.). Egypt. J. Microbiol 139, 129–139. https://doi.org/10.21608/ Vats, S., Gupta, T., 2017. Evaluation of bioactive compounds and antioxidant potential of
ejm.2017.1439.1027. hydroethanolic extract of Moringa oleifera Lam. from Rajasthan, India. Physiol. Mol.
Sangar, V.C., Samant, L.R., Pawar, S.S., Sadashiv, A., 2015. In silico approach to combat HIV Biol. Plants 23, 239–248. https://doi.org/10.1007/s12298-016-0407-6.
using Phytoconstituents of Moringa oleifera Lam. Immunol. Virol. 1, 1–25. Waiyaput, W., Payungporn, S., Issara-amphorn, J., 2012. Inhibitory effects of crude ex-
Schädler, S., Hildt, E., 2009. HBV life cycle: entry and morphogenesis. Viruses 1, 185–209. tracts from some edible Thai plants against replication of hepatitis B virus and
https://doi.org/10.3390/v1020185. human liver cancer cells. BMC Complement. Altern. Med. 12, 1–7.
Sebit, M.B., Chandiwana, S.K., Latif, A.S., Gomo, E., Acuda, S.W., Makoni, F., Vushe, J., 2000. WHO, 1980. Small pox is dead. World Health 1–40.
Quality of life evaluation in patients with HIV-I infection: the impact of traditional WHO, 2002. Hepatitis B. pp. 1–76.
medicine in Zimbabwe. Cent. Afr. J. Med. 46, 208–213. WHO, 2005. Traditional Medicine Strategy. pp. 1–59.
Semenya, S., Potgieter, M., Erasmus, L., 2012. Ethnobotanical survey of medicinal plants WHO, 2013. Traditional Medicine Strategy 2014–2023. pp. 1–76.
used by Bapedi healers to treat diabetes mellitus in the Limpopo Province, South Yoshida, H., Kai, H., Watanabe, W., Hagiwara, A., Sugita, C., Matsuno, K., Wadhwani, A.,
Africa. J. Ethnopharmacol. 141, 440–445. Kurokawa, M., Hidaka, M., 2016. Activation of cellular immunity in herpes simplex
Shinkafi, T.S., Bello, L., Hassan, S.W., Ali, S., 2015. An ethnobotanical survey of antidiabetic virus type 1-infected mice by the oral administration of aqueous extract of Moringa
plants used by Hausa–Fulani tribes in Sokoto, Northwest Nigeria. J. Ethnopharmacol. oleifera Lam. leaves. Phyther. Res. 30, 797–804. https://doi.org/10.1002/ptr.5580.
172, 91–99. Younus, I., Siddiq, A., Ishaq, H., Anwer, L., Badar, S., Ashraf, M., 2016. Evaluation of antiviral
Sivasankari, B., Anandharaj, M., Gunasekaran, P., 2014. An ethnobotanical study of indig- activity of plant extracts against foot and mouth disease virus in vitro. Pak. J. Pharm.
enous knowledge on medicinal plants used by the village peoples of Thoppampatti, Sci. 29, 1263–1268.
Dindigul district, Tamilnadu, India. J. Ethnopharmacol 153, 408–423.
Swayne, D.E., King, D.J., 2003. Avian influenza and Newcastle disease. J. Am. Vet. Med.
Assoc. 222, 1534–1540.