Available via license: CC BY 4.0
Content may be subject to copyright.
*Author for correspondence
JOURNAL OF NATURAL REMEDIES
DOI: 10.18311/jnr/2024/33171
Article Received on: 28.02.2023 Accepted on: 21.02.2024Revised on: 05.01.2024
REVIEW ARTICLE
An Evidence-based Systematic Review of
Pleiotropic Potential Health Benets of Sorghum
bicolor Supplement: A Polyphenol-rich Derivative
of the Leaf Sheaths of Sorghum Plant
Adaeze Adebesin1, Adrian Itivere Omogbiya2, Oluwafemi Gabriel Oluwole3,
Olajuwon Okubena4*, Rita Onyekachukwu Asomadu5, Michael O. S. Afolabi6,
Samira B. Lobo Makanjuola7, Louis Chukwuemeka Ajonuma8,
Adedoyin O. Dosunmu9, Ololade Otitoloju4 and Solomon Umukoro10
1Department of Pharmacology and Therapeutics, College of Health Sciences,
Olabisi Onabanjo University, Sagamu, Nigeria
2Department of Pharmacology, College of Health of Sciences, Delta State University, Abraka, Nigeria
3Department of Pathology, University of Cape Town, South Africa
4Health Forever Product Limited, Lagos, Nigeria; okubena@gmail.com
5Department of Biochemistry, University of Nigeria, Nsukka, Nigeria
6Department of Paediatrics and Community Medicine, University of Manitoba, Winnipeg, Canada
7Department of Pharmacology, Therapeutics and Toxicology, Lagos State University
College of Medicine, Ikeja, Lagos, Nigeria
8Department of Physiology, Lagos State University College of Medicine, Ikeja, Lagos, Nigeria
9Department of Haematology and Blood Transfusion, Lagos State University College of Medicine,
Ikeja, Lagos, Nigeria
10Neuropharmacology Unit, Department of Pharmacology and Therapeutics,
College of Medicine, University of Ibadan, Nigeria
Abstract
Globally, across different cultures, humans have historically depended largely on medicinal plants for managing diseases that
plants have been strongly attributed to the presence of secondary metabolites, particularly polyphenols. The potential
Sorghum bicolor-based Jobelyn Supplement (SBJS) have also
primary databases (PubMed, Europe PMC, and Cochrane Library), to identify published articles on therapeutic potentials
S. bicolor using the Preferred Reporting
S. bicolor; while ethnomedicinal surveys were on the therapeutic
S. bicolor published in the English language. The review provides valuable information
suggesting that SBJS possesses pleiotropic therapeutic potentials in diverse pathological conditions through mechanisms
684 An Evidence-based Systematic Review of Pleiotropic Potential Health Benets of Sorghum bicolor…
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
1. Introduction
Historically, human beings have responded to infectious
and non-infectious diseases that threaten their
health and existence through the use of plant-based
products which are available within their immediate
environment. In modern times, laboratory screening
of plant-based constituents has favourably shied the
therapeutic curve of modern medicines, as they have
yielded the discovery of important biomolecules with
activities such as anticancer (vincristine), antiglaucoma
(physostigmine), antimalarial (quinine), muscle
relaxant (tubocurarine), cardiotonic agent (digoxin),
and analgesic (morphine)1-3. Furthermore, the
discovery of calanolides (from Calophyllum teysmannii
Miq.) with anti-retroviral activity, paclitaxel (Taxus
brevifolia Nutt.) as an anticancer agent, artemisinin
(Artemisia annua L.) as an antimalarial, St. John’s wort
(Hypericum perforatum L.) as an antidepressant, and
ginseng (Panax ginseng C. A. Mey.) as an adaptogen
further demonstrate the key roles of medicinal plants
in contemporary healthcare1,4,5.
Over two decades ago, the WHO reported that
herbal products are extensively used across the globe
as alternatives to pharmaceutical medicines6. It was
estimated that about 80% of the African population
depends largely on herbs, as compared to 65% in India.
e WHO report also showed that 50% of Canadians
and 75% of people in France used alternative
medicines, while 85% of Japanese doctors prescribed
not only modern medicines but also traditional herbal
medicines6. In the United States of America, it has been
reported that over 15,000 herbal medicines are sold
annually for nearly ve billion dollars, thus constituting
the fastest-growing sector of the pharmaceutical
market6. ese reports further indicate the central
position of medicinal plants in primary healthcare
delivery.
Keywords:
Sorghum bicolor
e therapeutic ecacy of medicinal plants is
generally attributed to the presence of several potent
bioactive constituents, otherwise known as secondary
metabolites7-9. Various studies have established the
capability of several phytochemicals to attenuate the de-
regulation of the neuroendocrine–immune system that
orchestrates downstream activation of oxidative and
inammatory pathways - the primary co-conspirators
in the pathogenesis and progression of chronic
human diseases in response to infections or abiotic
factors7-9,10. us, it is widely believed that medicinal
plants with diverse phytochemical constituents with
proven antioxidant and anti-inammatory activities
may provide a better option for the treatment and
prevention of chronic diseases7,8,11.
e polyphenols, particularly avonoids and phenolic
acids, constitute a group of unique secondary metabolites
that play roles in the defence mechanisms of plants against
pathogenic attacks and abiotic factors8,12; for example, the
response of the Sorghum plant to pathogen attacks and
abiotic stressors leads to the accumulation of high levels
of secondary metabolites which enhance the survival
of the aected cells9,13. is defence mechanism is also
known to underpin the health-promoting benets of the
polyphenol-rich derivative of the leaf sheaths of the West
African variety of Sorghum bicolor-Jobelyn supplement
(SBJS). Indeed, SBJS has been widely acclaimed for its
several health benets, including chemoprevention
and mitigation of arthritic pains, stroke episodes,
and neuropsychiatric disorders, as well as promoting
resilience against stressful situations14-16. It has also been
reported to contain potent bioactive compounds17 with
multi-target and polyvalent pharmacological activities,
including suppression of oxidative and inammatory
signalling pathways8-9. ese bioactive constituents have
also been shown to exhibit neuroprotective abilities
and to inhibit cell proliferation in cancer cells through
review also showed that SBJS contains several bioactive substances with polyvalent pharmacological potentials including
modulation of pathological mechanisms involved in the mediation of aging and age-related diseases, such as arthritis,
insights gleaned from previous investigations on SBJS.
685
Adebesin et al.,
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
the stimulation of various apoptosis promoter genes, as
well as down-regulation of certain apoptosis inhibitor
genes, which are critical players in the induction of
carcinogenesis13,18. Moreover, the possible benets of
SBJS in chronic viral infections, such as HIV/AIDS and
COVID-19, have been envisaged based on its ability to
modulate the immune system by increasing the activity
of natural killer cells and activation of macrophages17.
is review seeks to provide experimental evidence
of the health-promoting pleiotropic eects of SBJS in
certain medical conditions, such as cancer, chronic
viral infections, stroke, arthritis, and premature aging.
e probable underpinning mechanisms relating to
its neuroprotective, antioxidant, anti-inammatory,
chemo-preventive, and immunomodulatory activities,
to elicit more robust studies and clinical trials on SBJS
concerning various associated medical conditions, are
also discussed.
2. Study Design and Search Strategy
Using the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA)19 standard, a
systematic search was conducted using three primary
databases (i.e., PubMed, Europe PMC, and Cochrane
Library), to identify and screen the published literature
on SBJS and West African variety of Sorghum bicolor.
e literature searches and analysis for selection and
quality assessment were performed between June 1
and July 8, 2022. e inclusion criteria were reviews,
experimental, clinical, and in vitro studies on SBJS and
the West African variety of Sorghum bicolor, as well as
ethnomedicinal surveys on the therapeutic use of the
West African variety of Sorghum bicolor published in
the English language. Articles describing the health
benets of polyphenols and their mechanisms of action
were also included. e exclusion criteria were plant-
based genome, and agricultural studies; studies that
merely cite SBJS and Sorghum bicolor-related papers
without being a primary study on them; clinical trials
whose results have not been published; and studies/
reviews/surveys that do not focus on SBJS or West
African variety of Sorghum bicolor.
2.1 Data Extraction and Synthesis
From the search terms selected from the three databases,
a total of 349 articles were identied. Duplicates were
removed manually. Two researchers reviewed the titles
and abstracts of the remaining 345 articles, aer which
an additional 258 articles were removed based on the
exclusion criteria. As a result, a total of 87 articles
were selected. Aer reviewing the full texts of these 87
articles, 46 were excluded based on the inclusion and
exclusion criteria, leaving only 41 articles. ese search
and selection steps are outlined in the PRISMA ow
diagram below (Figure 1).
3. Search Results
Of the 41 eligible articles found in the three databases,
3 were review papers (only 1, a mini-review, was
focused exclusively on SBJS), 5 were ethnomedicinal
surveys, 31 were experimental studies, and only 2
were clinical studies. ese ndings suggest that there
has not previously been a rigorous synthesis of the
extant literature on SBJS. erefore, it is against this
background that the present review seeks to present the
current state of research on SBJS.
Figure 1. PRISMA ow diagram for literature search.
686 An Evidence-based Systematic Review of Pleiotropic Potential Health Benets of Sorghum bicolor…
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
4. Discussion
Based on the 41 eligible articles retrieved from the three
databases and other relevant literature identied from
Google Scholar as a secondary source, the SBJS-related
data are presented, in terms of its source, phytoactive/
nutritional composition, potential therapeutic use in
the treatment of anaemic conditions, arthritis, stroke
disorders, chronic viral infections, and cancer, as
well as its use as an anti-aging supplement and as an
adaptogen.
4.1 Source of SBJS
As depicted in Figure 2, SBJS is obtained from the
polyphenol-rich leaf sheaths of the West African variety
of Sorghum bicolor L. Moench (Poaceae). S. bicolor,
commonly known as millet, sweet Sorghum, broom, or
guinea corn, is widely cultivated across many tropical
countries of the world for its economic, nutritional,
and medicinal values4-15. Accordingly, S. bicolor plant-
based regimens have been used for well over a century
in treating various ailments in traditional African
medical settings20,21. Folklore medical practices have
revealed that herbal concoctions of the root are used
as an antimalarial, especially by natives of Southern
Rhodesia, while the seed (grain)-based concoctions
are used to treat diarrhoea and breast cancer, as well
as for their anti-inammatory eects14,21. Extracts
from the stem are used as an anti-tubercular oedema
regimen, while the leaf is utilized for a wide range of
ailments9,14,21. Of particular note, the extract from the
leaf-sheaths portion of S. bicolor is known to exhibit
better therapeutic eects against diverse diseases over
those derived from other parts of the plant14.
It is instructive to note that SBJS has an FDA (USA)
GRAS certication with an organ systems tolerance
prole14,22,23. It has also gained local and international
recognition for the management of moderate to severe
anaemia (as in sickle cell patients), as well as cancer and
HIV/AIDS19,24. It is also widely used to combat stress
and to restore much-needed energy during periods of
recovery from debilitating diseases16. ere have been
reports that SBB is helpful in arthritis, cancer, and
neurological disorders such as stroke, psychosis, and
convulsions16. In addition, it is known to modulate
the immune system, enhance the body’s defence
mechanisms in response to stress and infections, and
aid recovery from debilitating illnesses16,17.
4.2 Phytoactive Constituents and
Nutritional Composition of SBJS
Some phytochemical studies have shown that
SBJS contains diverse bioactive polyphenol-rich
constituents, which can be broadly divided into
phenolic acids and avonoids. Polyphenols are the main
secondary metabolites known to exhibit antioxidant,
anti-inammatory, immunomodulatory, and
chemopreventive eects; the four key pillars of healthy
living and wellness9,25-27. It has been reported that all
food plants, such as cereals, fruits, and vegetables,
contain polyphenols in variable quantities9,27. e leaf
sheaths of the special domesticated West African variety
of the Sorghum plant have been documented as having
the highest concentrations of various polyphenols
(especially 3-deoxyanthocyanidin) among food
plants17. us, its unique properties have been ascribed
to its high polyphenol content, when compared with
other plant-based products. It is interesting to note
that these unique properties, among other scientic
reasons, explain its inclusion into the Drug Dictionary
of the National Cancer Institute, USA, where it
was described as a substance rich in polyphenols
and polyphenolic acids with the potential for
antioxidant, anti-inammatory, immunomodulatory,
and chemopreventive capabilities28. Specically,
the capability to modulate the immune system by
Figure 2. Sorghum bicolor plant with leaves, sheaths,
and nodes.
687
Adebesin et al.,
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
increasing the activity of Natural Killer (NK) cells and
the activation of macrophages was also ascribed to this
Sorghum-based supplement28.
High-performance liquid chromatography (HPLC)-
UV spectral characterization studies have revealed
that SBJS contains stabilized 3-deoxyanthocyanidin
(apigenindin and luteolinidin), luteolin (avone), and
naringenin (avone); see Table 1. us, avonoids are
the most bioactive polyphenolic compounds present in
SBJS15,17,29. A literature survey indicated that luteolin,
naringenin, and apigenin are the most-studied bioactive
avonoids present in SBJS, with diverse pharmacological
activities including anti-inammatory, antimutagenic,
anticancer, immunomodulatory, antioxidant,
and neuroprotective eects17,27,30. e richness
of 3-deoxyanthocyanidin in this Sorghum-based
supplement such as luteolinidin and apigeninidin has
also been implicated in the induction of apoptosis and
inhibition of cell proliferation in cancer cells through
the stimulation of various apoptosis promoter genes
and the downregulation of certain apoptosis inhibitor
genes. In addition, due to their strong antioxidant
nature, these compounds can scavenge free radicals
and prevent tissue damage17.
Besides, SBJS is also known to be very rich
in minerals such as iron, zinc, calcium, copper,
magnesium, selenium, phosphorus, sodium, and
potassium, which are essential for metabolism and
Table 1. Phytochemical constituents of leaf sheaths of Sorghum bicolor, Jobelyn®. It is reprinted/adapted with
permission from Makanjuola et al
688 An Evidence-based Systematic Review of Pleiotropic Potential Health Benets of Sorghum bicolor…
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
neuronal communication31. It is also rich in various
vitamins, including vitamin B12, niacin, and riboavin.
e presence of iron and vitamin B12 are clinically
relevant in anaemic and immune-related compromised
conditions32,33. It is also rich in proteins, fats,
carbohydrates, and omega-3 and -6 fatty acids. Omega-3
and -6 fatty acids, for example, have been recognized as
active promoters of anti-inammation, anti-apoptosis,
and modulation of neurotransmitter functions, as
well as functioning in the maintenance of cellular
membrane integrity and activation of neuroprotective
mechanisms34,35. e rich phytochemicals, minerals,
and vitamins with proven biological activities may
account for the diverse health benets of SBJS.
4.3 Potential Therapeutic Indications of
SBJS in Anaemic Conditions
e ability of SBJS to boost haemoglobin (Hb) content
and to cause rapid stimulation of the production
of Red Blood Cells (RBCs) has been reported in
literature15,19,24. is is particularly useful in reversing
anaemia and its symptomatic presentations, including
tiredness, dizziness, weakness, shortness of breath,
headaches, and fainting36. Anaemia is most common
in children, the elderly, and pregnant women36. e
main causes of decreased production of RBC and
Hb in anaemia include iron deciency, vitamin B12
deciency, and bone marrow tumours36. However,
factors responsible for the increased breakdown of RBC
have been identied to include genetic disorders such
as sickle cell anaemia, certain autoimmune diseases,
stressors including chronic infections (e.g., malaria
and HIV/AIDs), and haemolytic agents36,37. e
most common clinical approach for the treatment of
anaemia entails boosting RBC and Hb with iron, folic
acid, and vitamin B12 supplementation38,39. Drugs and
other agents that can stabilize RBCs may also be useful
in certain anaemic conditions, especially those due to
stressors such as chronic infections and exposure to
haemolytic agents37. Severe anaemia in Africa has been
described as a complex multi-factorial syndrome, for
which a single conventional intervention may not be
amenable37.
e blood-boosting capability of SBJS has been
observed in facilitating the treatment of moderate to
severe anaemia associated with sickle-cell disease,
cancer (e.g. leukaemia), malaria, and helminthiasis15,40.
Pre-clinical studies have shown that SBJS increased
RBC count, Hb content, and Packed Cell Volume (PCV)
in rats and rabbits infected with trypanosomes19,24.
Interestingly, some clinical studies have also
established its ecacy in anaemic conditions15,40,41. In
a randomized open-label clinical trial, it was reported
that SBJS increased RBC count, Hb content, and PCV in
women with pre-operative anaemic conditions without
inducing signicant changes in the white blood cell and
platelet counts41. Indeed, the prophylactic importance
of its use in anaemia has been well documented40,42,43.
e high concentration of iron in SBJS may be one
of the ways through which it increases Hb content and
PCV in clinical settings. e presence of vitamins B12,
niacin, and riboavin may also contribute to its blood-
rejuvenating eect and ability to combat anaemia in
chronic debilitating conditions, such as sickle cell
disease, malaria, and HIV/AIDs15,42. e presence of
omega-3 and -6 fatty acids, which are known for their
antioxidant eects and maintenance of cell membrane
integrity, might also act to protect RBCs from lysis
in pathological conditions. Interestingly, it has also
been found to protect RBCs against lysis induced by
hyposaline, suggesting the presence of phytochemicals
with a cytoprotective eect17,43. Additionally, oxidative
stress has been implicated in the aging of RBCs and
degradation of Hb molecules, which may contribute
to the anaemic condition in individuals with chronic
diseases44-47. us, its ecacy in anaemic conditions
may be related to the combined capacity to boost
Hb production and reduce oxidative stress in RBCs.
Nevertheless, more studies are necessary to elucidate
the exact mechanism(s) underlying its capacity to
boost RBC and Hb production in anaemic conditions
(Table 2).
4.4 Potential Benets of SBJS in Arthritic
Conditions
ere have been claims that SBJS is helpful in the
management of arthritic pain and other inammatory
conditions17,43. Arthritis is a common chronic
inflammatory disease, which is widely known to
impair the quality of life of the aected patients, and is
a major cause of disability among the elderly48-50. It is
characterized by chronic inflammation of the synovial
membrane, pain, and joint immobility48,51,52. Although
the pathogenesis of the disease is yet to be fully known,
689
Adebesin et al.,
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
the infiltration of inflammatory cells (leukocytes)
into the joints appears to play a prominent role in
the initiation of the tissue destruction in arthritic
condition50,52,53. e initiation and progression of the
disease have been closely connected with the migration
of inflammatory cells to the inflamed joint, in response
to the release of chemical mediators such as cytokines,
prostaglandins, and leukotrienes54-56. Furthermore, the
activity of the inflammatory cells triggers the release of
free radicals and other cytotoxic substances, including
pro-inammatory cytokines, which further enhance
joint tissue damage49-50,54.
e multi-dimensional nature of the disease,
therefore, suggests that a non-conventional approach
based on the use of agents with polyvalent actions
that can target the multiple mediators involved in
its pathology may be eective49,50. Interestingly,
several polyphenol-rich medicinal plants are being
investigated as new medicines for the treatment of
arthritis-related pains57,58. In this regard, SBJS has
been extensively studied in various in vitro and in vivo
models of inammation17,43,48. In a carrageenan model
of acute inammation, SBJS was shown to potentially
reduce inammatory paw oedema in rats43. is model
has served as one of the rational tools in the pre-clinical
screening of drugs with anti-inammatory properties,
as the reduction of paw oedema in rats is akin to the
attenuation of acute inammation in humans59. In
another study, SBJS was evaluated in the granuloma air
pouch model of sub-acute inammation. is model has
been shown to closely mimic the pathology of arthritic
disorders, based on the patterns of disease progression,
tissue destruction, inltration of White Blood Cells
(WBCs), and release of cytotoxic mediators54,60-62.
e ecacy of pharmacological ligands in the
granuloma air pouch model; is based on the reduction
of inammatory exudates, WBC count, concentrations
of biomarkers of oxidative stress, and inammatory
mediators in the uid exudates, as well as the histological
cyto-architecture of the pouch tissue61,62. Notably, SBJS
was reported to decrease the volume of inammatory
exudates, and WBC count, and positively modulated
the altered uid concentrations of biomarkers of
oxidative stress in rats. More importantly, histological
studies revealed that it also protected the pouch
tissue of the rats subjected to carrageenan-induced
granulomatous inammation43. ese ndings further
provide experimental evidence supporting its potential
in chronic inammatory diseases such as arthritis. is
observation has also been validated by the nding that
SBJS reduced the joint inammation, oxidative stress,
and pro-inammatory cytokines induced by Complete
Freund Adjuvant (CFA) in rodents48. It is important to
note that CFA-induced chronic inammation is a well-
recognized model for studying molecular mechanisms
associated with the pathophysiology of arthritis63,64.
e in vitro anti-inammatory activity of SBJS has
been evaluated using the rat RBC membrane stabilizing
model. e erythrocyte membrane is considered to be
similar to the lysosomal membrane, which plays an
important role in inammation65,66. is in vitro test is
known to be related to the release of haemoglobin from
RBCs exposed to hyposaline, and the prevention of
RBC lysis has been described as a biochemical index for
the evaluation of compounds with anti-inammatory
property65,66. us, compounds with membrane-
stabilizing capacity are expected to demonstrate anti-
inammatory activity by preventing the release of
lysosomal phospholipases, which are prime mediators
in the early phase of the inammatory process65,66.
us, the ndings that SBJS exhibited membrane-
stabilizing activity lend credence to its possession of
anti-inammatory eect and probable benecial eect
in combating inammatory diseases. Furthermore,
Benson et al.,17 also evaluated its in vitro anti-
inflammatory eect on cultured polymorphonuclear
cells and reported that it showed anti-inammatory
activity through mechanisms relating to suppression
of leukocyte migration and antioxidation. ey further
reported that its antioxidant protective capacity was
signicantly higher than that reported for various
cereal grains and vegetables17. is Sorghum-based
supplement was also shown to exhibit inhibitory
activity against a variety of oxidant molecules, with a
total Oxygen Radical Scavenging Capacity (ORAC)
of 37,622 μmol TE/g17. e authors concluded that it
also contained polyphenol-rich phytomolecules, such
as luteolin, naringenin, and apigenin, which have been
established as potent antioxidant and anti-inflammatory
compounds17. Similarly, ndings from the in vitro
studies of Mankanjuola et al.,29 have also revealed
that 7-methoxyavone-apigeninidin and apigenin
constituents of this Sorghum-based supplement
exhibited inhibitory activity against PG‐E2 expression
690 An Evidence-based Systematic Review of Pleiotropic Potential Health Benets of Sorghum bicolor…
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
and COX‐2 enzyme activity, further suggesting its role
in inammatory disorders (Table 2).
4.5 Potential Use of SBJS for Stroke
Disorders
ere is some evidence in the literature that has
established that the polyphenol-rich phytomoieties
found in SBJS exhibited a wide range of neuroprotective
eects against certain brain conditions, including
stroke. It has been suggested that its protective eect
against ischemic stroke might be related to several
mechanisms, including inhibition of NF-kB signalling
pathway67-69. It is worth noting that ischemic stroke
is a fatal disease caused by sudden obstruction of
cerebral blood ow and subsequent neuronal cell
death67,70,71. Occlusion of the carotid artery and the
attendant reperfusion are critical factors involved in
ischemic stroke67,70,71. e morbidity and mortality
associated with stroke are alarming, resulting in huge
losses of economic manpower and productivity72-74.
Stroke is typically associated with neurological decits
with accompanying physical disabilities, and the belief
that it is incurable may also lead to various psychiatric
disturbances, such as anxiety, depression, and memory
decits75.
Ischemic stroke accounts for over 85% of all cases
of stroke and its pathology is known to be due to
activation of neuronal oxidative and inammatory
pathways67,76. Both pre-clinical and clinical studies
have reported increased biomarkers of oxidative stress
and inammatory cytokines aer the onset of ischemic
stroke67,76. Interleukin-6 (IL-6), interleukin-1 (IL-1),
and tumour necrosis factor-alpha (TNF-α) are some
of the most studied cytokines in stroke pathology67,77.
In stroke patients, IL-6 has been linked to early
neurological deterioration, greater infarct volumes,
and poorer long-term outcomes67. High plasma
levels of TNF-α have also been correlated with infarct
volume and neurological decits in various models of
cerebral ischemia67,76. During reperfusion, there is an
increase in serum cortisol, which further exacerbates
neuronal damage by disrupting glucose homeostasis
and increasing oxidative stress in the brain. Moreover,
increased oxidative stress and leukocyte inltration
result in the formation of more pro-inammatory
cytokines, which perpetuate neurodegeneration in
the brains of animals with ischemic stroke67,76,77. On
this basis, current approaches to the treatment of the
disease using thrombolytic agents are quite limited in
scope, as they cannot antagonize the injurious oxidative
and inammatory events that underpin ischemic
stroke67,68,78. us, oxidative and neuro-inammatory
pathways are currently being viewed as promising
targets for the development of new drugs that could
be used to antagonize the multiple mechanisms and
mediators involved in ischemic brain injury. Bioactive
compounds of plant origin with potent antioxidant
and anti-inammatory activities are believed to
hold promise for the development of therapeutic
strategies67,68,78,79.
Indeed, several studies have shown that various
phytochemicals can target the multiple pathways
involved in the pathophysiology of stroke, including
oxidative stress, inammation, and apoptotic cell death.
Moreover, epidemiological data in the extant literature
have evidenced that regular consumption of food rich
in polyphenols can reduce the risk of stroke78,79. e
eect of SBJS has been experimentally evaluated against
ischemic stroke using the occlusion of the bilateral
common carotid artery by a group of scientists at the
University of Ibadan, Nigeria16. e results of their
investigations revealed that the neurological decits
produced by the occlusion of the bilateral common
carotid artery in rats—which approximates the
clinical characteristics seen in patients with ischemic
stroke80, were attenuated by SBJS16. In addition, it
also mitigated the biochemical changes relating to
increases in oxidative biomarkers and depletion of
antioxidant defence molecules in the brains of the rats
subjected to the ischemic stroke16. e brain contents
of pro-inammatory cytokines (IL-6 and TNF-α)
and the expression of immunopositive cells of NF-kB
in rats with ischemic stroke were reduced by SBJS16.
e neuroprotective eect of this Sorghum-based
supplement is another major nding obtained from
this study. It is well-known that stroke causes damage
to several neuronal pathways, which are crucial in the
regulation of motor and cognitive functions67,68. us,
the nding that SBJS protected the neurons of the
striatum, prefrontal cortex, and hippocampus, as well
as increasing the population of viable neuronal cells
in these brain regions of ischemic rats, corroborates
its neuroprotective capacity. However, robust clinical
trials using neurological and molecular markers are
691
Adebesin et al.,
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
necessary to establish its clinical ecacy in stroke
(Table 2).
4.6 Anti-aging Potential of SBJS
Aging has been described as a universal and multi-
factorial process characterized by a gradual decline
of physiological functions. It occurs at the molecular,
cellular, and tissue levels, and comprises a series
of pathological mechanisms such as deregulated
autophagy, mitochondrial dysfunction, telomere
shortening, oxidative stress, systemic inammation,
and metabolic dysfunction81-83. e deregulation
of these interconnected pathways leads cells to a
state of senescence, which contributes to aging and
age-related diseases. Although many theories have
been proposed to explain the molecular mechanism
associated with the aging process, the free radical
theory, proposed by Harman84 in 1956, appears
to be highly insightful. According to this theory,
aging is associated with the accumulation of reactive
oxygen species that exert oxidative damage to cellular
biomolecules and apoptosis, ultimately leading to a
decline of physiological function and death82-84. e
cellular degeneration and early apoptosis caused by
free radicals produce oxidative stress, which has been
regarded as the main pathological culprit in premature
aging82,84. Moreover, oxidative stress is oen aggravated
by a variety of stressors, such as chronic infections and
abiotic factors, which may accelerate aging and age-
related diseases, as well as increased vulnerability to
death. e deterioration in bodily function with aging
is the primary risk factor for most human pathologies,
such as cancer, diabetes, cardiovascular disorders, and
neurodegenerative diseases78,85.
Strategic focus on interventions that increase
lifespan in model organisms such as Drosophila
melanogaster, and the potential of translating such
discoveries into the development of therapies to combat
age-related diseases, are currently being pursued78.
Such interventions that are capable of slowing aging
are likely to delay the onset of many human diseases,
such as cancer, diabetes, cardiovascular disorders,
and neurodegenerative diseases. In this regard, the
consumption of foods rich in polyphenols has been
reported to have probable preventive and therapeutic
implications in the aforementioned non-communicable
diseases86-88. Recently, food plants rich in polyphenols
have been described as the ‘Elixir of Life’, as they possess
the capabilities of promoting longevity78.
e eectiveness of the anti-aging action of
nutritional interventions has been advocated in the war
against age-related diseases, promoting healthy living
and longevity81. Mechanistically, natural supplements
have been shown to exhibit polyvalent actions against
oxidative, inammatory, and degenerative processes,
ultimately aiding immune functions and, thus,
improving quality of life. Indeed, food supplements
with antioxidant-boosting capacity have been gaining
attention for the prevention and treatment of chronic
conditions linked to Reactive Oxygen Species (ROS), as
they have relevant properties related to age-related and
chronic syndromes78,86-88.
e probable anti-aging potentials of SBJS lie in its
antioxidant, anti-inammatory, anti-apoptotic, and
neuroprotective eects in experimental models22,43,89.
Studies have shown that its polyphenolic constituents
such as apigenin and luteolin exhibit anti-aging activity
through neuroprotective mechanisms relating to
anti-inammatory, antioxidant, and anti-apoptosis
eects78,82,90. Interestingly, the rst concrete evidence
regarding its anti-aging eect came from a study
conducted at Brunswick Laboratory, USA, which
revealed that it inhibited the activity of elastase-1 and
collagenase-115: enzymes that have been implicated
in premature aging, especially, the aging of the skin91.
Specically, SBJS was shown to be more eective than
vitamin C and ferulic acid in inhibiting collagenase
and elastase, suggesting its capability to promote skin
health15. Also, its potential in age-related diseases,
such as Alzheimer’s disease, has been investigated in
a scopolamine-induced amnesia model92. e study
revealed that it also attenuated amnesia produced by
scopolamine through its neuronal antioxidant protective
mechanisms92. A more recent study using Drosophila
melanogaster showed that the supplement extended
the lifespan and improved motor function of the ies,
through augmentation of the antioxidant status93. In
addition, it also extended the lifespan of D. melanogaster
exposed to lipopolysaccharide (LPS)92. In another
study, SBJS was shown to exhibit a neuroprotective
capability against neurodegeneration in a binge-alcohol
rat model through modulation of cellular apoptosis
(p53) neurotrophin-positive expression and decreased
inammatory signalling cascade in specic brain
692 An Evidence-based Systematic Review of Pleiotropic Potential Health Benets of Sorghum bicolor…
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
regions22,89. ese experimental ndings lend further
credence to its potential in promoting cellular survival
and longevity (Table 2).
4.7 Potential of SBJS in Chronic Viral
Infections
e probable benecial eects of SBJS in chronic viral
infections, such as HIV/AIDS and COVID-19, have
been envisaged based on its potent anti-inammatory
capacity, as well as its ability to modulate the immune
system by increasing the activity of natural killer cells
and activation of macrophages15,17. e pathogenesis
of HIV is known to be associated with the depletion
of the immune function, which predisposes infected
individuals to secondary infections94,95, with the ensuing
immunocompromised state threatening survival95-97.
Although the impact of COVID-19 infection is closely
related to chronic inammation, commonly described
as the cytokine storm97, the severity of the disease also
depends on the functionality of the immune system96,97.
e pattern of invasion and infectivity is also similar
to HIV, as the SARS-CoV-2 virus exhibits receptor
attachment, cellular entry, replication, cellular outlet,
and cytokine induction94-97. e complex nature of HIV
and COVID-19 suggests a need for the development of
interventions with polyvalent actions that can mitigate
the inammatory mediators while also strengthening
the immune system against viral replication and
infectivity97,98. In this regard, the therapeutic potentials
of several polyphenolic compounds in controlling the
key cellular mechanisms involved in the infectivity of
these viral infections are actively being investigated97.
is is not surprising, as polyphenols are well-known
to modulate the immune response and boost resistance
to chronic viral infections15,17,26,97,99.
e anti-inammatory, antioxidant, and
immunomodulatory eects of SBJS15,17,42 are strongly
indicative of its anti-viral potential against HIV/AIDs
and COVID-19. Pre-clinical studies have shown that
SBJS up-regulates the expressions of chemokines
and increases CD4 cell counts in cultured human
monocytes and macrophages41, which are known to be
severely aected by HIV infection17,95,100. Specically,
Benson et al.,17 have shown that SBJS causes several
folds increase in the expression of chemokines (e.g.,
RANTES/CCL5, Mip-1a/CCL3, and MIP-1b/CCL4)
known to inhibit HIV entry into CD4+ T-cells.
Interestingly, increases in chemokine production exert
protective eects on the host immune response against
HIV infection and disease progression95,100. It was
also reported to exert an immunomodulatory eect
on a wide range of both pro- and anti-inammatory
cytokines, such as IL-1β, IL-6, IL-8 and TNF-α and,
in particular, interferon-α17, suggesting eective viral
suppressive capabilities in patients with HIV/AIDs95,96.
It has also been reported that it increased interferon-
alpha (IFN-α) levels by 12-fold17, further suggesting
immunomodulatory and viral suppressive capacities.
It is important to note that IFN-α has been reported
to inhibit HIV replication95. Interestingly, naringenin
- one of the prominent phytoactive constituents of
SBJS - has been reported to show strong inhibition of
SARS-CoV-2 infection in vitro101. e inhibition of
pro-inammatory cytokines, such as IL-6 and TNF-α,
by naringenin has been ascribed to a synergistic action
that enhances its antiviral eects101. us, the potential
benets of naringenin in COVID-19 may be ascribed
to its ability to inhibit or slow down the viral infection
and the associated cytokine release/cytokine storm
syndrome101. It is interesting to note that the leaf
sheaths of Sorghum bicolor - the principal source of SBJS
- have been listed as one of the plants used for treating
respiratory infections in an ethnomedicinal survey102,
lending further credence to its therapeutic potential in
COVID-19. Indeed, Alhazmi et al.,103 have reported
that S. bicolor is one of the medicinal plants from which
molecules with potential benet against viral diseases,
such as COVID-19, have been extracted103. From
a broader perspective, SBJS is therefore, a potential
chemo-preventive agent for modulating the immune
function and controlling inammatory reactions in
the context of viral infections, such as HIV/AIDs
and COVID-19. Clinical studies have shown that it
increased the CD4+ T-lymphocyte cellular count as
well as bone marrow function, indicating a potential
benet in HIV/AIDS15,39 (Table 2).
4.8 Cancer Chemopreventive Potential of
SBJS
e bioactive constituents of SBJS are known to inhibit
cell proliferation in cancer cells through the stimulation
of various apoptotic promoter genes, as well as down-
regulating certain apoptotic inhibitor genes that are
critical in carcinogenesis104. It is worth noting that
693
Adebesin et al.,
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
cancer is a disease of multiple pathologies, though
dysregulated or abnormal cell replication appears to be
the primary underlying factor105,106. Cancer may ensue
as a result of critical alterations in DNA at the site of
some classes of genes that are important in regulating
cell proliferation, cell death, and DNA repair, as well
as tumour-suppressing genes105,106. Damage to DNA
repair genes is a major predisposing factor leading to
mutations in the genome, ultimately increasing the
probability of neoplastic transformations105,106. Cancer
formation involves three major phases: initiation,
promotion, and progression (Figure 3). e stage of
initiation is a rapid, irreversible change in the genetic
machinery of the target cell that primes it for subsequent
neoplasm. is early phase of carcinogenesis is known
to be due to exposure to mutagenic carcinogens, which
interact with the DNA to form permanent heritable
change(s) in the genome that are yet to be expressed
phenotypically105,106. is suggests that initiation
alone does not result in tumour formation; however,
initiated cells display altered cellular characteristics,
which may include altered responsiveness to the
microenvironment and a proliferative advantage,
relative to the surrounding normal cells105,106.
e stage of promotion has been described as a
reversible process in the life cycle of the cancer cell,
which usually entails the conversion of initiated
cells into active proliferation to a greater extent than
normal cells105,106. An essential feature of tumour
promotion is the creation of a mitogenic environment
and enhancement of the possibility for further genetic
damage105,106. It has been reasoned that polyphenols
with multiple actions capable of targeting the various
pathways that trigger the promotion of initiated/
latent cells to active proliferation may retard tumour
development10,107,108. is suggests the importance
of polyphenol-rich foods with chemopreventive
capabilities. e nal phase of cancer progression
is characterized by the development of irreversible
neoplasm, manifested as a rapid increase in tumour
size, with the cells undergoing further mutations with
invasive and metastatic potentials105,106,108. Although
the ecacy of phytochemicals might be limited at
this last phase, there have been several claims of the
eectiveness of dietary polyphenols against a variety
of tumours. Epidemiological and animal studies have
shown that phenolic compounds exhibit anti-cancer
properties through multiple mechanisms relating to
antioxidant activity, induction of cell cycle arrest and
apoptosis, and the promotion of tumour suppressor
proteins7,10,109.
Epidemiological studies have also reported that
Sorghum consumption is correlated with a low
incidence of oesophageal cancer in various parts of
the world10,109-111. Park et al.,112 have reported that the
metastasis of breast cancer to the lungs was blocked
by Sorghum extracts in an immune-decient mouse
metastasis model. In vitro studies of Sorghum extracts
on several cancer cells have revealed induction of cell
apoptosis, inhibition of cell proliferation, and promotion
of the expression of cell cycle regulators13,18,104,107. e
eects of phenolic extracts from 13 Sorghum accessions
on cancer cell growth on both hepatocarcinoma
HepG2 and colorectal adenocarcinoma Caco2 cell lines
have recently been investigated7. It was concluded that
the phenolic extracts of various Sorghum accessions
Figure 3. Phases of Carcinogenesis: Initiation, promotion, progression, and metastasis reprinted/adapted from
Siddiqui et al108.
694 An Evidence-based Systematic Review of Pleiotropic Potential Health Benets of Sorghum bicolor…
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
inhibited HepG2 or Caco-2 cancer cell growth
in a dose- and time-dependent manner, through
cytostatic and apoptotic mechanisms7. e anticancer
properties of Sorghum extracts have been ascribed
partly to the high content of 3-deoxyanthocyanidins13.
Moreover, Makanjuola et al.,113 have reported that
the 7-methoxyavone-apigeninidin and apigenin
constituents of SBJS exhibited anticancer potential
through the modulation of immune cells in in vitro
models. is echoes the description by the National
Cancer Institute of SBJS as the richest source of
3-deoxyanthocyanidins; indeed, it has the highest
contents of various polyphenolic compounds among
food plants, with high capability for chemoprevention
and inhibition of cell proliferation28. Although more
studies on the potential anticancer ecacy of SBJS
are necessary, the existing information suggests its
valuable benets as a supplement for cancer prevention
(Table 2).
4.9 Potential of SBJS as Adaptogen
e routine use of SBJS in an adaptogenic-like fashion
for the relief of feelings of intense stress and to restore
much-needed energy during periods of recovery from
debilitating diseases represents another major reason
for its routine use16,20,24. It is important to note that
the response to both biotic (pathogens) and abiotic
(physical and psychosocial factors) stressors induces
adaptive responses; however, when stress persists
and becomes intense, the adaptive mechanisms
of the organism become decient, resulting in the
pathogenesis of several human diseases114-116. e
breakdown in adaptive responses, which signals organ
pathologies and immune dysfunctions, was coined by
Hans Selye as general adaptation syndrome8,117,118,
who reasoned that human illnesses stemmed from
ineective adaptation118. e notion of general
adaptation syndrome led to the search during the
Second World War by Russian scientists for substances
- later called adaptogens - of plant origin that could be
used to enhance the capability for physical and mental
work, and which can help individuals to survive in
challenging situations involving intense/prolonged
stress117,119.
Adaptogens were initially dened as substances
that enhance the "state of non-specic resistance"
to stress; a physiological condition that is linked
with dysregulation of the neuroendocrine–immune
system117,119. More recently, adaptogens were dened
as a category of herbal medicinal and nutritional
products promoting the adaptability, resilience, and
survival of living organisms in stressful situations8.
us, adaptogens are meant to stimulate the intrinsic
adaptive mechanisms of the organism, to help it
survive in situations of intense/prolonged stress117.
e most striking features of adaptogens include the
capability to mount resistance against varied stressors,
such as physical, chemical, biological (pathogens),
and psychological noxious factors, thus exerting
benecial healthy eects independent of the nature of
the pathological conditions117,119. However, in clinical
settings, adaptogens are generally reputed for their
ability to exert an anti-fatigue eect, increasing mental
work capacity against a background of stress and
fatigue, particularly concerning tolerance to mental
exhaustion and enhanced attention117.
Extensive reviews have documented the ability
of adaptogenic substances to activate the protective
mechanisms of cells, to promote increased survival
rates in both in vitro and in vivo models8,117. Adaptogens
have been reported to eectively prevent and treat
stress-related and aging disorders, such as chronic
fatigue, memory impairment, depression, anxiety,
sleep disturbance, diabetes, heart diseases, chronic
inammatory and autoimmune diseases, infections,
and cancer8. Based on the polyvalent pharmacological
actions of adaptogens, it has been proposed that the
normal paradigm of "one drug for one disease: does
not correctly apply to them8. Plants with known
adaptogenic actions include Panax ginseng, Withania
somnifera (L.) Dunal, Glycyrrhiza glabra L., Asparagus
racemosus Willd., Ocimum sanctum L., Piper longum L.,
Tinospora cordifolia (unb.) Miers, Emblica ocinalis
Gaertn., Rhodiola rosea L., Schisandra chinensis (Turcz.)
Baill., and Eleutherococcus senticosus8.
e rst concrete experimental evidence of the
potential adaptogenic-like activity of SBJS was based
on its reported ability to bring about relief concerning
feelings of intense stress and as an energizer in the
context of general body weakness16,20,24. Its adaptogenic
potential has also been demonstrated in Unpredictable
Chronic Mild Stress (UCMS) through neuroprotective
mechanisms relating to the suppression of oxidative
stress and pro-inammatory cytokines120. It is worthy
695
Adebesin et al.,
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
of note to understand that UCMS mimics how humans
encounter multiple stressors daily, and is generally
accepted as the most suitable model for elucidation of
the pathological mechanisms of chronic stress-induced
organ pathologies and immune dysfunctions. In the
UCMS model, SBJS attenuated the loss of neuronal cells
in the Cornu Ammonis 3 (CA3) of the hippocampus,
suggesting a neuroprotective eect120. Moreover, it
also reduced serum corticosterone concentrations120, a
major biomarker of chronic stress response. It is well-
known that cortisol-induced activation of oxidative
stress and inammatory pathways is the primary culprit
involved in the mediation of stress-related pathologies8.
Indeed, an elevated concentration of cortisol serves
as a key biomarker of intense stress. Substances with
adaptogenic activity have been shown to reduce serum
concentrations of corticosterone8. us, the ability of
SBJS to reduce corticosterone further suggests that it
has an adaptogenic-like property120. e possibility
of this supplement behaving like an adaptogen is also
based on ndings that it attenuated depression-like
symptoms in mice subjected to stressful situations
(i.e., forced swimming exercise and tail suspension
protocols)121. In an in vitro stress model, it was also
reported that SBJS protected RBCs against hyposaline-
induced haemolysis43, suggesting cytoprotection and
increased cellular resistance to stress. Notably, the
recent nding that it increased the survival rate and
prolonged the lifespan of ies exposed to LPS further
reinforced its potential adaptogenic-like property93.
is is in agreement with previous reports linking
adaptogens to increased lifespan and stress resistance
in C. elegans122; another model organism widely used
for the elucidation of the neurobiological mechanisms
of stress and age-related disorders. e capability of this
Sorghum-based supplement to combat stress in various
models may be related to the presence of minerals,
vitamins, and phytochemicals that can modulate the
key mediators of stress response and immune defence
mechanisms in response to stressors. ese sets of
reports are suggestive of its capability to mitigate stress
in healthy individuals (Table 2).
4.10 Future Perspectives and Direction for
Further Studies
is systematic review provides evidence-
based information on the health benets of SBJS
associated with its well-known anti-oxidative, anti-
inammatory, immunomodulatory, chemopreventive
and neuroprotective activities. Nevertheless, there
is still a need for more robust experimental studies
to understand the exact molecular mechanisms of
action of SBJS and how some of its components may
act synergistically and/or antagonistically, either when
used alone or in combination with food or other drugs.
Insights gained from such studies will determine
Table 2. Major pharmacological activities of SBJS
Sl. No. Major pharmacological eect of SBJS References
1. Boost blood volume in moderate to severe anaemic conditions 20,40,41
2. Demonstrated in vitro and in vivo anti-inammatory activity, and immune-modulating eect 17,43,29
3. Reduces neurological decits and pro-inammatory cytokines, and
NF-ĸB signalling pathway in rats with ischemic stroke
16
4. Exhibited neuroprotective eect in alcoholic rats via alterations in GFAP and NF protein
expressions
22
5. Anti-tumour, antiviral and immune-modulating properties 17,40,113
6. Attenuated inammatory responses and neurobehavioural decits in complete Freund-adjuvant-
induced arthritis in mice
48
7. Reduces neuronal degeneration via modulation of p53 and ɤ-Enolase protein expressions in the
prefrontal cortex of rats exposed to ethanol
87
8. Demonstrated anti-amnesic eect in rodents through its antioxidant property 90
9. Demonstrated antidepressant-like properties in mice 121
10. Exhibited adaptogenic property in the unpredictable chronic mild stress model 120
11. Extended the life span and improves motor function in Drosophila melanogaste via augmentation
of antioxidant status
91
696 An Evidence-based Systematic Review of Pleiotropic Potential Health Benets of Sorghum bicolor…
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
whether this supplement can continue to be used as a
standalone supplement, or if some of its components
may be isolated and clinically matched with specic
pathological conditions. It is also important to identify
other possible components. For instance, while SBJS is
prepared from the leaf sheaths of S. bicolor, a 2 kD, the
cationic, amphipathic, and virucidal peptide has been
isolated from Sorghum seeds, which binds and masks
essential viral envelope proteins123-125. As such, it is
important to determine whether the same protein is
present in So rghum’s leaf sheaths and, if so, to evaluate
its concentration and investigate what contributory
role (in terms of antagonistic or synergistic activities)
the peptide may play in the potential health benets of
SBJS.
Finally, the limited clinical studies on SBJS
underscore the need to clinically evaluate its
therapeutic potential in specic disease conditions,
including arthritis, cancer, chronic viral infections,
and stroke, through rigorous clinical trials. is is
especially important in a developing African context,
where the high cost of conventional therapies hinders
drug compliance and contributes to disease-related
morbidity and mortality. e results from such clinical
trials are necessary, as they are expected to provide the
evidential strength that researchers need to signicantly
reduce some of the barriers to the clinical adoption of
validated indigenous phytomedicines126 in mainstream
medical practice.
5. Conclusion
is systematic review provides updated information
on experimental and clinical studies on the health
benets of SBJS, a unique herbal supplement derived
from the polyphenols-rich leaf sheaths of Sorghum plant
in diverse pathological conditions including arthritis,
stroke and cancer. e ndings that it also increased
the activity of natural killer cells and up-regulated the
expression of chemokines; and also inhibited the release
of pro-inammatory cytokines suggest that it might be
useful in infectious diseases such as HIV/AIDS and
COVID-19. Some clinical studies have also shown its
therapeutic potential in the management of moderate
to severe anaemia in patients with HIV/AIDs and sickle
cell disease. is review also documented experimental
evidence, which suggests that it has adaptogenic-like
properties through multiple mechanisms relating to the
suppression of oxidative and inammatory pathways.
ese ndings may perhaps support its usefulness in
the relief of feelings of intense stress and weakness
experienced during periods of debilitating illnesses.
6. References
1. Cragg GM, Newman DJ. Natural products drug discovery
in the next millennium. Pharmaceutical Biol. 2001; 39:8-17.
https://doi.org/10.1076/phbi.39.s1.8.0009 PMid:21554167
2. Soejarto DD. Biodiversity prospecting and benet-sharing:
Perspectives from the eld. J Ethnopharmacol. 1996;
51:1-15. https://doi.org/10.1016/0378-8741(95) 01345-8
PMid:9213606
3. Balandrin MF, Kinghorn AD, Farnsworth NR. Plant-derived
natural products in drug discovery and development: An
overview. In: Kinghorn AD, Balandrin MF editors. Human
Medicinal Agents from Plants. Washington DC American
Chemical Society; 1993. p. 2-12. https://doi.org/10.1021/
bk-1993-0534.ch001
4. Ellis JM, Reddy P. Eects of Panax ginseng on quality of
life. Ann Pharmacother. 2002; 36(3):75-79. https://doi.
org/10.1345/aph.1A245 PMid:11895046
5. Josey ES, Tackett RL. St. John’s wort: A new alternative for
depression? Int J Clin Pharm. 1999; 37:111-19.
6. Aschwanden C. Herbs for health but how safe are they?
Bulletin of the World Health Organization. 2001; 79:691-2.
7. Chen X, Shen J, Xu J, Herald T, Smolensky D, Perumal R, et
al. Sorghum phenolic compounds are associated with cell
growth inhibition through cell cycle arrest and apoptosis in
human hepatocarcinoma and colorectal adenocarcinoma
cells. Foods. 2021; 10(5). https://doi.org/10.3390/
foods10050993 PMid:34062914 PMCid:PMC8147257
8. Panossian AG, Eerth T, Shikov AN, Pozharitskaya
ON, Kuchta K, Mukherjee PK, et al. Evolution of the
adaptogenic concept from traditional use to medical
systems: Pharmacology of stress‐ and aging‐related disease.
Med Res Rev. 2021; 41:630-703. https://doi.org/10.1002/
med.21743 PMid:33103257 PMCid:PMC7756641
9. Espitia-Hernández P, Mónica L, González C, Ascacio-
Valdés JA, Dávila-Medina D, Flores-Naveda A, et al.
Sorghum (Sorghum bicolor L.) as a potential source of
bioactive substances and their biological properties. Crit
Rev Food Sci. 2002; 62:2269-80. https://doi.org/10.1080/1
0408398.2020.1852389 PMid:33280412
10. Cox S, Noronha L, Herald T, Bean S, Lee SH, Perumal R,
et al. Evaluation of ethanol-based extraction conditions
of Sorghum bran bioactive compounds with downstream
anti-proliferative properties in human cancer cells.
697
Adebesin et al.,
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
Heliyon. 2019; 5. https://doi.org/10.1016/j.heliyon.2019.
e01589 PMid:31111105 PMCid:PMC6512580
11. Duthie GG, Duthie SJ, Kyle JAM. Plant polyphenols in
cancer and heart disease: Implications as nutritional
antioxidant. Nutr Res Rev. 2000; 13:79-106. https://doi.
org/10.1079/095442200108729016 PMid: 19087434
12. Yahfou N, Alsadi N, Jambi M, Matar C. e
immunomodulatory and anti-inammatory role of
polyphenols. Nutrients. 2018; 10. https://doi.org/10.3390/
nu10111618 PMid:30400131 PMCid:PMC6266803
13. Devi PS, Saravanakumar M, Mohandas S. Identication of
3-deoxyanthocyanins from red Sorghum (Sorghum bicolor)
bran and its biological properties. Afr J Pure Appl Chem.
2011; 5:181-93.
14. Adebayo AH, Yakubu OF, Egbung GE, Williams OI,
Okubena O. Sub-acute toxicological eects of Jobelyn
on pregnant albino rats. American Inst Phy. 2018; 1954.
https://doi.org/10.1063/1.5033398
15. Okubena O, Makanjuola S, Ajonuma LC, Dosunmu A,
Umukoro S, Erah PO. e West African Sorghum bicolor
leaf sheath extract Jobelyn® and its diverse therapeutic
potentials. MOJ Drug Des Dev er. 2018; 2:1-10.
16. Umukoro S, Oghwere EE, Ben-Azu B, Owoeye O, Ajayi
AM, Omorogbe O, et al. Jobelyn® ameliorates neurological
decits in rats with ischemic stroke through inhibition
of release of pro-inammatory cytokines and NF-ĸB
signaling pathway. Pathophysio. 2018; 26(1):77-88. https://
doi.org/10.1016/j.pathophys.2018.10.002 PMid:30413288
17. Benson KF, Beaman JL, Ou B, Okubena A, Okubena O,
Jensen GS. West African Sorghum bicolor leaf sheaths have
anti-inammatory and immune-modulating properties in
vitro. J Med Food. 2013; 16:230-8. https://doi.org/10.1089/
jmf.2012.0214 Mid:23289787 PMCid:PMC3598435
18. Woo HJ, Oh LT, Lee JY, Jun DY, Seu MC, Woo KS, et al.
Apigeninidin induces apoptosis through activation of
Bak and Bax and subsequent mediation of mitochondrial
damage in human promyelocytic leukemia HL-60
cells. Process Biochem. 2012; 47:1861-71. https://doi.
org/10.1016/j.procbio.2012.06.012
19. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Homann
TC, Mulrow CD, et al. e PRISMA 2020 statement: An
updated guideline for reporting systematic reviews. Br Med
J. 2021; 372. https://doi.org/10.1136/bmj.n71
20. Okochi VI, Okpuzor J, Okubena MO, Awoyemi AK. e
inuence of African herbal formular on the haematological
parameters of trypanosome infected rats. Afr J Biotechnol.
2003; 2:312-16. https://doi.org/10.5897/AJB2003.000-1064
21. Awika JM, Rooney LW. Sorghum phytochemicals and
their potential impact on human health. Phytochem.
2000; 65:1199-221. https://doi.org/10.1016/j.phytochem.
2004.04.001 PMid:15184005
22. Oyinbo CA, Dare WN, Avwioro OG, Igbigbi PS.
Neuroprotective eect of Jobelyn in the hippocampus of
alcoholic rat is mediated in part by alterations in GFAP and
NF protein expressions. Adv Biol Sci Res. 2015; 9:305-17.
23. Eniojukan JF, Aina BA. Toxicological proles of commercial
herbal preparation, Jobelyn. Int J Health Res. 2009; 2:369-
74. https://doi.org/10.4314/ijhr.v2i4.55438
24. Erah PO, Asonye CC, Okhamafe AO. Response of
Trypanosomabrucei-induced anaemia to a commercial
herbal preparation. Afr J Biotech. 2003; 2:307-11. https://
doi.org/10.5897/AJB2003.000-1063
25. Nnaji M. How an African-made dietary supplement
promises to revolutionize medical treatment. e African
Courier [Internet]. 2016. [cited 2022 Sep 23]. Available
from: https://www.theafricancourier.de/news/africa/
jobelyn-how-a-nigerian-made-drug-promises-to-mix-up-
things-in-medical-treatment/
26. Paraiso IL, Revel JS, Stevens JF. Potential use of polyphenols
in the battle against COVID-19. Curr Opin Food Sci. 2020;
32:149-55. https://doi.org/10.1016/j.cofs.2020.08.004
PMid:32923374 PMCid:PMC7480644
27. Xu H, Wang E, Chen J, Xiao J, Wan M. Neuroprotective
phytochemicals in experimental ischemic stroke:
Mechanisms and potential clinical applications. Oxid Med
Cell Longev. 2021. https://doi.org/10.1155/2021/6687386
PMid:34007405 PMCid:PMC8102108
28. Drug Dictionary of National Cancer Institute, USA.
Sorghum bicolor supplement [Internet]. n.d. [cited
2023 Feb 12]. Available from: https://www.cancer.gov/
publications/dictionaries/cancer-drug/def/sorghum-
bicolor-supplement
29. Makanjuola SBL, Ogundaini AO, Ajonuma LC, Dosunmu
A. Apigenin and apigeninidin isolates from the Sorghum
bicolor leaf targets inammation via cyclooxygenase‐2
and prostaglandin‐E2 blockade. Clin Transplant. 2018;
21:1487‐95. https://doi.org/10.1111/1756-185X.13355
PMid:30146750
30. Kim J, Fann DY, Seet RC, Jo DG, Mattson MP, Arumugam
TV. Phytochemicals in ischemic stroke. Neuromolecular
Med. 2016; 18:283-305. https://doi.org/10.1007/s12017-
016-8403-0 PMid:27193940
31. Shayganfard M. Are essential trace elements eective in
modulation of mental disorders? Update and perspectives.
Biol Trace Elem Res. 2022; 200:1032-59. https://doi.
org/10.1007/s12011-021-02733-y PMid:33904124
32. Roth W, Mohamadzadeh M. Vitamin B12 and gut-brain
homeostasis in the pathophysiology of ischemic stroke.
eBio Medicine. 2021; 73. https://doi.org/10.1016/j.
ebiom.2021.103676 PMid:34749301 PMCid:PMC8586745
33. Tamura J, Kubota K, Murakami B, Sawamura M,
Matsushima T, Tamura T, et al. Immunomodulation by
vitamin B12: Augmentation of CD8+ T lymphocytes
698 An Evidence-based Systematic Review of Pleiotropic Potential Health Benets of Sorghum bicolor…
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
and natural killer (NK) cell activity in vitamin B12-
decient patients by methyl-B12 treatment. Clin Exp
Immunol. 2001; 116:28-32. https://doi.org/10.1046/j.1365-
2249.1999.00870.x PMid:10209501 PMCid:PMC1905232
34. Djuricic L, Calder PC. Benecial outcomes of omega-6
and omega-3 polyunsaturated fatty acids on human
health: An update for 2021. Nutrients. 2021; 13.
https://doi.org/10.3390/nu13072421 PMid:34371930
PMCid:PMC8308533
35. Tantipaiboonwong P, Chaiwangyen W, Suttajit M, Kangwan
N, Kaowinn S, Khanaree C, et al. Molecular mechanism of
antioxidant and anti-inammatory eects of omega-3 fatty
acids in perilla seed oil and rosmarinic acid rich fraction
extracted from perilla seed meal on TNF-α induced A549
lung adenocarcinoma cells. Molecules. 2021; 26. https://
doi.org/10.3390/molecules26226757 PMid:34833849
PMCid:PMC8622939
36. Janz TG, Johnson RL, Scott D, Rubenstein SD. Anemia
in the emergency department: Evaluation and treatment.
Emerg Med. Pract. 2013; 15:1-15.
37. van Hensbroek MB, Jonker F, Bates L. Severe acquired
anaemia in Africa: New concepts. Br J Haematol.
2011; 154:690-95. https://doi.org/10.1111/j.1365-
2141.2011.08761.x PMid:21707575
38. West CE. Strategies to control nutritional anaemia. Am
J Clin Nutr. 1996; 64:789-90. https://doi.org/10.1093/
ajcn/64.5.789 PMid:8901803
39. Low MS, Speedy J, Styles CE, De-Regil LM, Pasricha SR. Daily
iron supplementation for improving anaemia, iron status
and health in menstruating women. Cochrane Database
Syst Rev. 2016; 4. https://doi.org/10.1002/14651858.
CD009747.pub2 PMid:27087396
40. Ayuba GI, Jensen GS, Benson KF, Okubena AM, Okubena
O. Clinical ecacy of a West African Sorghum bicolor-
based traditional herbal preparation Jobelyn shows
increased hemoglobin and CD4+ T-lymphocyte counts
in HIV-positive patients. J Altern Complement Med.
2014; 20(1):53-6. https://doi.org/10.1089/acm.2013.0125
PMid:24283768 PMCid:PMC3904510
41. Tayo AO, Dosunmu AO, Akinola IO, Adewunmi A, Oloyede
OA, Akinbami AA, et al. Makanjuola SBL. An open-label,
randomized, parallel-group comparative study of the
ecacy of Sorghum bicolor extract in preoperative anemia.
Nutrition. 2007; 33:113-17. https://doi.org/10.1016/j.
nut.2016.05.005 PMid:27461168
42. Archer N, Galacteros F, Brugnara C. Clinical trials update
in sickle cell anaemia. Am J Hematol. 2015; 90:934-
50. https://doi.org/10.1002/ajh.24116 PMid:26178236
PMCid:PMC5752136
43. Umukoro S, Oluwole OG, Eduviere AT, Omogbiya IA, Ajayi
AM. Jobelyn exhibited anti-inammatory, antioxidant, and
membrane-stabilizing activities in experimental models. J
Basic Clin Physiol Pharmacol. 2015; 26:501-8. https://doi.
org/10.1515/jbcpp-2014-0113 PMid:26020554
44. Barodka VM, Nagababu E, Mohanty JG, Nyhan D,
Berkowitz DE, Riind JM, et al. New insights provided by
a comparison of impaired deformability with erythrocyte
oxidative stress for sickle cell disease. Blood Cell Mol
Dis. 2013. https://doi.org/10.1016/j.bcmd.2013.10.004
PMid:24246527
45. Nagababu E, Mohanty JG, Bhamidipaty S, Ostera GR,
Riind JM. Role of the membrane in the formation of
heme degradation products in red blood cells. Life Sci.
2010; 86:133-8. https://doi.org/10.1016/j.lfs.2009.11.015
PMid:19958781 PMCid:PMC2819203
46. Wang C, Zennadi R. e role of RBC oxidative stress
in sickle cell disease: From the molecular basis to
pathologic implications. Antioxidants. 2021; 10. https://
doi.org/10.3390/antiox10101608 PMid:34679742
PMCid:PMC8533084
47. Mohanty JG, Nagababu E, Riind JM. Red blood cell
oxidative stress impairs oxygen delivery and induces
red blood cell aging. Front Physiol. 2014. https://doi.
org/10.3389/fphys.2014.00084 PMCid:PMC3937982
48. Omorogbe O, Ajayi AM, Ben-Azu B, Oghwere EE, Adebesin
A, Aderibigbe AO, et al. Jobelyn® attenuates inammatory
responses and neuro behavioural decits associated with
complete Freund-adjuvant-induced arthritis in mice.
Biomed Pharmacother. 2018; 98:585-93. https://doi.
org/10.1016/j.biopha.2017.12.098 PMid:29288974
49. Choy E. Understanding the dynamics: Pathways involved
in the pathogenesis of rheumatoid arthritis. Rheumatology.
2012; 51:3-11. https://doi.org/10.1093/rheumatology/
kes113 PMid:22718924
50. García-González A, Gaxiola-Robles R, Zenteno-Savín T.
Oxidative stress in patients with rheumatoid arthritis. Rev
Invest Clin. 2015; 67:46-53.
51. Muller-Ladner U, Pap T, Gay RE, Neidhart M, Gay S.
Mechanisms of disease: e molecular and cellular basis
of joint destruction in rheumatoid arthritis. Nat Clin
Pract Rheum. 2005; 1:102-10. https://doi.org/10.1038/
ncprheum0047 PMid:16932639
52. Hernández-Hernández V, Ferraz-Amaro I, Díaz-González
F. Inuence of disease activity on the physical activity
of rheumatoid arthritis patients. Rheumatology. 2014;
53:722-31. https://doi.org/10.1093/rheumatology/ket422
PMid:24369410
53. Hitchon, CA, El-Gabalawy HS. Oxidation in rheumatoid
arthritis. Arthritis Res er. 2004; 6:265-78. https://doi.
org/10.1186/ar1447 PMid:15535839 PMCid:PMC1064874
54. Winrow VR, Winyard PG, Morris CJ, Blake DR. Free
radicals in inammation: second messengers and
mediators of tissue destruction. Br Med Bull. 1993;
699
Adebesin et al.,
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
49:506-22. https://doi.org/10.1093/oxfordjournals.bmb.
a072627 PMid:8221019
55. Jones A, Al-Janabi M, Solanki K, Snack PR, Greenwood
A, Doyle D, Britton KM, Huskisson E. In vivo leukocyte
migration in arthritis. Arthritis Rheumatol. 1991; 34:270-5.
https://doi.org/10.1002/art.1780340304 PMid:2003853
56. Yudoh K, Karasawa R, Masuko K, Kato T. Water-soluble
fullerene (C60) inhibits the development of arthritis in the
rat model of arthritis. Int J Nanomedicine. 2009; 4:217-
25. https://doi.org/10.2147/IJN.S7653 PMid:19918368
PMCid:PMC2775692
57. Rangan U, Bulkley GB. Prospects for treatment of free
radical-mediated tissue injury. Br Med Bull. 1993; 49:700-
18. https://doi.org/10.1093/oxfordjournals.bmb.a072641
PMid:8221033
58. Frech TM, Clegg DO. e utility of nutraceuticals in the
treatment of osteoarthritis. Curr Rheumatol Rep. 2007;
9:25-30. https://doi.org/10.1007/s11926-007-0018-x
PMid:17437663
59. Winter CA, Risley EA, Nuss GW. Carrageenan induced
edema in hind paw of the rat as an assay for anti-
inammatory drugs. Proc Soc Exp Biol Med. 1962;
111:544-7. https://doi.org/10.3181/00379727-111-27849
PMid:1400 1233
60. Benitz KF, Hall LM. e carregeenin-induced abscess, a
new test for anti-inammatory activity of steroids and non-
steroids. Arch Int Pharmacodyn er. 1969; 144:185-95.
61. Boris A, Stevenson RH. e eects of some non-steroidal
anti-inammatory agents on carrageenin-induced exudate
formation. Arch Int Pharmacodyn er. 1965; 153:205-9.
62. Pearson CM, Wood FD. Studies of polyarthritis and other
lesions induced in rats by injection of mycobacterial
adjuvant. General clinical and pathological characteristics
and some modifying factor. Arthritis Rheumatol.
1969; 2:440-59. https://doi.org/10.1002/1529-0131(195
910)2:5<440::AID-ART1780020510>3.0.CO;2-N
63. Newbould BB. Chemotherapy of arthritis induced in rats
by mycobaterial adjuvant. Br J Pharmacol Chemother.
1963; 21:127-36. https://doi.org/10.1111/j.1476-5381.1963.
tb01508.x PMid:14066137 PMCid:PMC1703866
64. ShindeUA, Phadke AS, Nair AM, Mungantiwar AA,
Dikshit VJ, Saraf MN. Membrane stabilizing activity: a
possible mechanism of action for the anti-inammatory
activity of Cedrusdeodara wood oil. Fitoterapia. 1999;
70:251-7. https://doi.org/10.1016/S0367-326X(99)00030-1
65. Gadamsetty G, Maru S, Sarada NC. Antioxidant and anti-
inammatory activities of the methanolic leaf extract of
traditionally used medicinal plant Mimusops elengi L.
J Pharm Sci. 2013; 5:125-30.
66. Anrather J, Iadecola JC. Inammation and stroke: An
overview. Neurotherapeutics. 2016; 13:661-70. https://
doi.org/10.1007/s13311-016-0483-x PMid:27730544
PMCid:PMC5081118
67. Boslett J, Hemann C, Zhao YJ, Le e H, Zweier JL. Luteolinidin
protects the postischemic heart through CD38 inhibition
with preservation of NAD(P)(H). J Pharmacol Exp er.
2017; 36:99-108. https://doi.org/10.1124/jpet.116.239459
PMid:28108596 PMCid:PMC5363772
68. Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms
of ischemic brain damage. Neuropharmacology. 2008;
55:310. https://doi.org/10.1016/j.neuropharm.2008.01.005
PMid:18308346 PMCid:PMC2603601
69. Lipton P. Ischemic cell death in brain neurons. Physiol
Rev. 1999; 79:1431-568. https://doi.org/10.1152/
physrev.1999.79.4.1431 PMid:10508238
70. Adeloye D. An estimate of the Incidence and prevalence
of stroke in Africa: A systematic review and meta-analysis.
PLoS One. 2014; 9. https://doi.org/10.1371/journal.
pone.0100724 PMid:24967899 PMCid:PMC4072632
71. Ramsey LE, Siegel JS, Lang CE, Strube M, Shulman
GL, Corbetta M. Behavioural clusters and predictors
of performance during recovery from stroke. Nat Hum
Behav. 2017; 1. https://doi.org/10.1038/s41562-016-0038
PMid:28713861 PMCid:PMC5508212
72. Feigin VL, Norrving B, George MG, Foltz JL. Prevention of
stroke: A strategic global imperative. Nat Rev Neurol. 2016;
12:501-12. https://doi.org/10.1038/nrneurol.2016.107
PMid:27448185 PMCid:PMC8114177
73. Edward CJ. Ischemic Stroke: An acute onset syndrome.
Neurol. 2017; 17:1-16.
74. Petrovic-Djergovic D, Goonewardena SN, Pinsky
DJ. Inammatory disequilibrium in stroke. Circ
Res. 2016; 119:142-58. https://doi.org/10.1161/
CIRCRESAHA.116.308022 PMid:27340273 PMCid:
PMC5138050
75. Zhang H, Gao W, Qian T, Tang J, Li J. Transcription factor
changes following long term cerebral ischemia/reperfusion
injury. Neural Regen Res. 2013; 8.
76. Meccariello B, D’Angelo S. Impact of polyphenolic-food
on longevity: An elixir of life. An Overview. Antioxidants.
2021; 10. https://doi.org/10.3390/antiox10040507
PMid:33805092 PMCid:PMC8064059
77. Chen Y, Jui-Sheng W, Yang S, Huang C, Chang C, Sun GY,
Lin T. Stroke, angiogenesis and phytochemicals. Front
Biosci. 2012; S4:599-610. https://doi.org/10.2741/s287
PMid:22202079
78. Simret B, Litrus L, Soriano L, Monbureau M, To LK,
Braithwaite SP, et al. A Pharmacological screening approach
for discovery of neuroprotective compounds in ischemic
stroke. PLoS One. 2013; 8. https://doi.org/10.1371/journal.
pone.0069233 PMid:23874920 PMCid:PMC3715457
79. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer
G. e hallmarks of aging. Cell. 2013; 153:1194-217.
700 An Evidence-based Systematic Review of Pleiotropic Potential Health Benets of Sorghum bicolor…
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
https://doi.org/10.1016/j.cell.2013.05.039 PMid:23746838
PMCid:PMC3836174
80. de Almeida AJO, Ribeiro TP, de Medeiros IA.
Aging: Molecular pathways and implications on the
cardiovascular system. Oxid Med Cell Longev. 2017.
https://doi.org/10.1155/2017/7941563 PMid:28874954
PMCid:PMC5569936
81. Riera CE, Merkwirth C, Filho CDDM, Dillin A. Signaling
networks determining life span. Annu. Rev Biochem.
2018; 85:35-64. https://doi.org/10.1146/annurev-biochem-
060815-014451 PMid:27294438
82. Harman D. Aging: A theory based on free radical and
radiation chemistry. J Gerontol. 1996; 11:298-300. https://
doi.org/10.1093/geronj/11.3.298 PMid:13332224
83. Jarrett SG, Boulton ME. Consequences of oxidative stress in
age-related macular degeneration. Mol Aspects Med. 2012;
33:399-417. https://doi.org/10.1016/j.mam.2012.03.009
PMid:22510306 PMCid:PMC3392472
84. Sachdeva V, Roy A, Bharadvaja N. Current prospects of
nutraceuticals: A review. Curr Pharm Biotechnol. 2010;
21:884-96. https://doi.org/10.2174/1389201021666200130
113441 PMid:32000642
85. Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini
M, Borges G, Crozier A. Dietary (poly) phenolics in
human health: Structures, bioavailability, and evidence
of protective eects against chronic diseases. Antioxid
Redox Signal. 2013; 18:1818-92. https://doi.org/10.1089/
ars.2012.4581 PMid:22794138 PMCid:PMC3619154
86. Cory H, Passarelli S, Szeto J, Tamez M, Mattei J. e role of
polyphenols in human health and food systems: A mini-
review. Front Nutr. 2018; 5:87. https://doi.org/10.3389/
fnut.2018.00087 PMid:30298133 PMCid:PMC6160559
87. Oyinbo CA, Igbigbi PS, Avwioro OG. Jobelyn supplement
lowered neuronal degeneration: Signicance of altered
p53 and ɤ-Enolase protein expressions in prefrontal cortex
of rat exposed to ethanol. Ann Neurosci. 2016; 23:139-
48. https://doi.org/10.1159/000449179 PMid:27721582
PMCid:PMC5043160
88. Leri M, Scuto M, Ontario ML, Calabrese V, Calabrese
EJ, Bucciantini M, Stefani M. Healthy eects of plant
polyphenols: Molecular mechanism. Int J Mol Sci. 2020;
21. https://doi.org/10.3390/ijms21041250 PMid:32070025
PMCid:PMC7072974
89. ring T, Hili P, Naughton D. Anti-collagenase, anti-
elastase and anti-oxidant activities of extracts from 21
plants. BMC Complement Med er. 2009; 9. https://doi.
org/10.1186/1472-6882-9-27 PMid:19653897 PMCid:
PMC2728709
90. Umukoro S, Ugbomah A, Aderibigbe A, Omogbiya A.
Antioxidant property of Jobelyn® as the possible mechanism
underlying its anti-amnesic eect in rodents. Basic Clin
Neurosci. 2013; 4:42-9.
91. John R, Abolaji AO, Adedara AO, Ajayi AM, Aderibigbe
AO, Umukoro S. Jobelyn® extends the life span and improves
motor function in Drosophila melanogaster exposed to
lipopolysaccharide via augmentation of antioxidant status.
Metab Brain Dis. 2022; 37:1031-40. https://doi.org/10.1007/
s11011-022-00919-4 PMid:35156155
92. Chun TW, Fauci AS. HIV reservoirs: pathogenesis
and obstacles to viral eradication and cure. AIDS.
2012; 26(10):1261-8. https://doi.org/10.1097/
QAD.0b013e328353f3f1 PMid:22472858
93. Naif H. Pathogenesis of HIV infection. Infect Dis Rep. 2013;
6. https://doi.org/10.4081/idr.2013.s1.e6 PMid:24470970
PMCid:PMC3892619
94. Yazdanpanah F, Hamblin MR, Rezaei N. e immune
system and COVID-19: Friend or foe? Life Sci. 2020; 256.
https://doi.org/10.1016/j.lfs.2020.117900 PMid:32502542
PMCid:PMC7266583
95. Goc A. Phenolic compounds disrupt spike-mediated
receptor-binding and entry of SARS-CoV-2 pseudo-virions.
PLoS One. 2021; 16. https://doi.org/10.1371/journal.
pone.0253489 PMid:34138966 PMCid:PMC8211150
96. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution
of the novel coronavirus from the ongoing Wuhan
outbreak and modeling of its spike protein for risk of
human transmission. Life Sci. 2020; 63:457-60. https://
doi.org/10.1007/s11427-020-1637-5 PMid:32009228
PMCid:PMC7089049
97. Verma S, Twilley D, Esmear T, Oosthuizen CB, Reid
AM, Nel M, Lall N. Anti-SARS-CoV natural products
with the potential to inhibit SARS-CoV-2 (COVID-19).
Front Pharmacol. 2020; 11. https://doi.org/10.3389/
fphar.2020.561334 PMid:33101023 PMCid:PMC7546787
98. Alkhatib G, Bombardier C, Broder CC, Feng Y, Kennedy PE,
Murphy PM, et al. CC CKR5: A RANTES, MIP-1alpha, IP-
1beta receptor as a fusion cofactor for macrophage-tropic
HIV. Science. 1996; 272:1955-8. https://doi.org/10.1126/
science.272.5270.1955 PMid:8658171
99. Scagnolari C, D’Amore A, Palombi F, Criscuolo E, Frasca
F, Pierangeli A, et al. Naringenin is a powerful inhibitor
of SARS-CoV- 2 infection in vitro. Pharmacol Res.
2021; 163. https://doi.org/10.1016/j.phrs.2020.105255
PMid:33096221 PMCid:PMC7574776
100. Lawal LO, Olufade II, Rau BO, Aremu AO.
Ethnobotanical survey of plants used for treating cough
associated with respiratory conditions in Ede South local
government area of Osun State, Nigeria. Plants. 2020; 9.
https://doi.org/10.3390/plants9050647 PMid:32443771
PMCid:PMC7286022
101. Alhazmi HA, Najmi A, Javed SA, Sultana S, Al Bratty M,
Makeen HA, et al. Medicinal plants and isolated molecules
demonstrating immunomodulation activity as potential
alternative therapies for viral diseases including COVID-1.
701
Adebesin et al.,
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
Front Immunol. 2021; 12. https://doi.org/10.3389/
mmu.2021.637553 PMid:34054806 PMCid:PMC8155592
102. Devi PS, Kumar MS, Das SM. Evaluation of antiproliferative
activity of red Sorghum bran anthocyanin on a human
breast cancer cell line (mcf-7). Int J Breast Cancer. 2011.
https://doi.org/10.4061/2011/891481 PMid:22312562
PMCid:PMC3262581
103. Pitot HC. e molecular biology of carcinogenesis.
Cancer. 1993; 72:962-70. https://doi.org/10.1002/
1097-0142(19930801)72:3+<962::AID-CNCR2820
721303>3.0.CO;2-H PMid:8334671
104. Oliveira PA, Colaço A, Chaves R, Guedes-Pinto H, Luis F,
De-La-Cru P, Lopes C. Chemical carcinogenesis. An Acad
Bras Cienc. 2007; 79:593-616. https://doi.org/10.1590/
S0001-37652007000400004 PMid:18066431
105. Smolensky D, Rhodes D, McVey DS, Fawver Z, Perumal
R, Herald T, et al. High-polyphenol Sorghum bran extract
inhibits cancer cell growth through ROS induction, cell
cycle arrest, and apoptosis. J Med Food. 2018; 21:990-8.
https://doi.org/10.1089/jmf.2018.0008 PMid:29733262
106. Siddiqui LA, Sanna V, Ahmad N, Sechi M, Mukhtar H.
Resveratrol nano formulation for cancer prevention and
therapy. Ann N Y Acad Sci. 2015; 134:20-31. https://doi.
org/10.1111/nyas.12811 PMid:26109073
107. Xu S, Shen Y, Xu J, Qi G, Chen G, Wang G, et al. Antioxidant
and anticancer eects in human hepatocarcinoma (HepG2)
cells of papain-hydrolyzed Sorghum karin hydrolysate.
J Funct Foods. 2019; 58:374-82. https://doi.org/10.1016/j.
j.2019.05.016
108. Van Rensburg SJ. Epidemiologic and dietary evidence for
a specic nutritional predisposition to esophageal cancer. J
Natl Cancer Inst. 1981; 67:243-51.
109. Isaacson C. e change of the staple diet of black South
Africans from Sorghum to maize (corn) is the cause of the
epidemic of squamous carcinoma of the oesophagus. Med
Hypotheses. 2005; 64:658-60. https://doi.org/10.1016/j.
mehy.2004.09.019 PMid:15617883
110. Park JH, Darvin P, Lim EJ, Joung YH, Hong DY, Park EU,
et al. Hwanggeumchal Sorghum induces cell cycle arrest,
and suppresses tumor growth and metastasis through Jak2/
STAT pathways in breast cancer xenogras. PLoS ONE.
2012; 7. https://doi.org/10.1371/journal.pone.0040531
PMid:22792362 PMCid:PMC3391253
111. Makanjuola SBL, Dosunmu D, Ajonuma L, Ogundaini A,
Okubena O. Newly isolated compounds from West African
Sorghum bicolor leaf sheaths Jobelyn® show potential in
cancer immunosurveillance. J Cancer Res er. 2016; 4:31-
7. https://doi.org/10.14312/2052-4994.2016-6
112. deKloet ER, Joels M, Holsboer F. Stress and the brain: From
adaptation to disease. Nat Rev Neurosci. 2005; 6:463-75.
https://doi.org/10.1038/nrn1683 PMid:15891777
113. McEwen BS, Biron CA, Brunson KW, Bulloch K, Chambers
WH, Dhabhar FS, et al. e role of adrenocorticoids as
modulators of immune function in health and disease:
Neural, endocrine and immune interactions. Brain Res
Rev. 1997; 23:79-133. https://doi.org/10.1016/S0165-
0173(96)00012-4 PMid:9063588
114. McEwen BS, Gray JD, Nasca C. Recognizing resilience:
Learning from the eects of stress on the brain.
Neurobiol Stress. 2015; 1:1-11. https://doi.org/10.1016/j.
ynstr.2014.09.001 PMid:25506601 PMCid:PMC4260341
115. Panossian A, Wikman G. Evidence-based ecacy of
adaptogens in fatigue, and molecular mechanisms related to
their stress-protective activity. Curr Clin Pharmacol. 2009;
4:198-219. https://doi.org/10.2174/157488409789375311
PMid:19500070
116. Selye H. e general adaptation syndrome and disease
of adaptation. J Clin Endocrinol Metab. 1946; 6:117-230.
https://doi.org/10.1210/jcem-6-2-117 PMid:21025115
117. Brekhman II, Dardymov IV. New substances of plant origin
which increase nonspecic resistance. Annu Rev Pharmacol
Toxicol. 1968; 8:419-30. https://doi.org/10.1146/annurev.
pa.09.040169.002223 PMid:4892434
118. Umukoro S, Omorogbe O, Aluko OM, Eduviere TA, Owoeye
O, Oluwole OG. Jobelyn, a Sorghum-based nutritional
supplement attenuates unpredictable chronic mild stress-
induced memory decits in mice. Behav Brain Sci. 2015;
5:586-97. https://doi.org/10.4236/jbbs.2015.513056
119. Umukoro S, Eduviere AT, Aladeokin AC, Olugbemide A.
Antidepressant-like property of Jobelynan African unique
herbal formulation in mice. Drug Res. 2014; 64:146-50.
https://doi.org/10.1055/s-0033-1354366 PMid:24002928
120. Wiegant FA, Surinova S, Ytsma E, Langelaar-Makkinje M,
Wikman G, Post JA. Plant adaptogens increase lifespan
and stress resistance in C. elegans. Biogerontology. 2009;
10:27-42. https://doi.org/10.1007/s10522-008-9151-9
PMid:18536978
121. Simnadis TG, Tapsell LC, Beck EJ. Eect of sorghum
consumption on health outcomes: A systematic review.
Nutr Rev. 2016; 74:690-707. https://doi.org/10.1093/nutrit/
nuw036 PMid:27694643
122. Boas LC, Campos ML, Berlanda EL, de CarvalhoNeves
N, Franco OL. Antiviral peptides as promising
therapeutic drug. Cell Mol Life Sci. 2019; 76. https://
doi.org/10.1007/s00018-019-03138-w PMid:31101936
PMCid:PMC7079787
123. Mammari N, Krier Y, Albert Q, Devocelle M, Varbanov M.
Plant-derived antimicrobial peptides as potential antiviral
agents in systemic viral infections. Pharmaceuticals.
2021; 14(8):774. https://doi.org/10.3390/ph14080774
PMid:34451871 PMCid:PMC8400714
124. Afolabi MO. Resolving the identity dilemmas of Western
healthcare in Africa: Towards ethical and pragmatic
702 An Evidence-based Systematic Review of Pleiotropic Potential Health Benets of Sorghum bicolor…
Journal of Natural Remedies | eISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 24 (4) | April 2024
approaches. Culture and Dialogue. 2020; 8:147-65. https://
doi.org/10.1163/24683949-12340080
125. Mammari N, Krier Y, Albert Q, Devocelle M, Varbanov M.
Plant-derived antimicrobial peptides as potential antiviral
agents in systemic viral infections. Pharmaceuticals.
2021; 14(8):774. https://doi.org/10.3390/ph14080774
PMid:34451871 PMCid:PMC8400714
126. 126. Afolabi MO. Resolving the identity dilemmas
of Western healthcare in Africa: Towards ethical and
pragmatic approaches. Culture and Dialogue. 2020; 8:147-
65. https://doi.org/10.1163/24683949-12340080