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Enema et al. European Journal of Pharmaceutical and Medical Research
www.ejpmr.com │ Vol 11, Issue 7, 2024. │ ISO 9001:2015 Certified Journal │
41
A REVIEW OF THE ANTIINFLAMMATORY AND ANALGESIC CONSTITUENTS OF
THE FAMILY ANNONACEAE
Enema O. J.1*, Umoh U. F.1, Johnny I. I.1 and Igwe M. N.2
1Department of Pharmacognosy and Natural Medicine, Faculty of Pharmacy, University of Uyo, Uyo, Nigeria.
2Department of Pharmacognosy, Faculty of Pharmacy, Madonna University, Elele, Rivers State, Nigeria.
Article Received on 06/05/2024 Article Revised on 27/05/2024 Article Accepted on 17/06/2024
INTRODUCTION
Inflammation is the body's innate response to harmful
stimuli, such as pathogens, damaged cells, or irritants.
While it is a protective mechanism aimed at eliminating
the initial cause of cell injury, clearing out necrotic cells
and tissues, and initiating tissue repair, chronic
inflammation can lead to various diseases, including
arthritis, diabetes, and cancer. Pain, a complex
experience associated with tissue damage, often
accompanies inflammation. Managing inflammation and
pain is, therefore, crucial for improving quality of life
and treating various health conditions.[1]
The exploration of medicinal plants for therapeutic
purposes has been a cornerstone of pharmaceutical
discovery, offering promising avenues for novel anti-
inflammatory and analgesic treatments. Among these,
the Annonaceae family, a diverse group of species
widely distributed across tropical and subtropical
regions, has garnered scientific interest for its significant
ethnopharmacological applications. Traditionally,
various cultures have harnessed the therapeutic potentials
of Annonaceae species, utilizing them in folk medicine
to alleviate pain and inflammatory conditions. This
historical use underscores the importance of
investigating the family's bioactive compounds for
modern therapeutic applications.[2],[3]
The Annonaceae family, which has over 2,000 species,
including the well-known genera Annona, and Xylopia,
has been used in traditional medicine across different
cultures to treat a myriad of health issues. Many species
within this family have been reported to possess anti-
inflammatory and analgesic properties, drawing the
attention of researchers aiming to validate and
understand the traditional uses of these plants.[4]
SJIF Impact Factor 7.065
Review Article
ISSN 2394-3211
EJPMR
EUROPEAN JOURNAL OF PHARMACEUTICAL
AND MEDICAL RESEARCH
www.ejpmr.com
ejpmr, 2024, 11(7), 41-54
ABSTRACT
Inflammatory and pain-related disorders constitute a significant global health burden, often treated with synthetic
drugs that can elicit adverse side effects. The Annonaceae family, a botanical group traditionally employed in
various cultures for its therapeutic properties, has shown potential as a source of natural anti-inflammatory and
analgesic agents. This review paper aims to critically evaluate the scientific literature on the anti-inflammatory and
analgesic properties of the Annonaceae family to consolidate current knowledge, highlight research gaps, and
suggest directions for future research. The methodology of this review involved a systematic search of databases
for studies on Annonaceae species, focusing on their reported uses in traditional medicine and the scientific
validation of these uses. Studies were included if they provided data on the phytochemical content,
pharmacological activities, and mechanisms of action related to anti-inflammatory and analgesic effects. The
results indicate that several species within the Annonaceae family contain bioactive compounds, such as
acetogenins, alkaloids, and essential oils, which exhibit significant anti-inflammatory and analgesic activities.
Some notable examples include Annona muricata, Annona senegalensis, and Annona squamosa, which have been
documented for their potential in treating a variety of inflammatory and painful conditions. Pharmacological
screenings have provided evidence supporting the traditional uses of these plants, demonstrating their effectiveness
in reducing inflammation and pain in both in vivo and in vitro studies. The Annonaceae family shows great
promise as a natural source of anti-inflammatory and analgesic compounds. However, more rigorous scientific
studies, including clinical trials, are essential to fully understand the therapeutic potential and safety profile of these
plant species. This review underscores the need for further exploration of Annonaceae species, to develop safer,
natural alternatives to synthetic drugs for the management of pain and inflammation.
KEYWORDS: Annonaceae, anti-inflammatory, chemical constituents, pharmacological activities.
*Corresponding Author: Enema O. J.
Department of Pharmacognosy and Natural Medicine, Faculty of Pharmacy, University of Uyo, Uyo, Nigeria.
Enema et al. European Journal of Pharmaceutical and Medical Research
www.ejpmr.com │ Vol 11, Issue 7, 2024. │ ISO 9001:2015 Certified Journal │
42
The search for natural anti-inflammatory and analgesic
agents is propelled by the ongoing need to address side
effects associated with synthetic drugs and the global
burden of inflammatory and pain-related disorders. The
identification of plant-derived compounds with these
properties offers a sustainable and potentially less
adverse alternative to conventional treatments. In this
context, the Annonaceae family presents a rich
repository of chemical entities, with several species
having been documented for their anti-inflammatory and
analgesic effects through preliminary pharmacological
screenings,[5],[6]
Millions of people worldwide deal with chronic pain and
inflammation daily, conditions that significantly reduce
the quality of life and increase healthcare costs. While
modern medicine offers various treatments, including
synthetic drugs, for these ailments, these solutions often
come with undesirable side effects such as dependency
and long-term health risks. This dilemma underscores the
urgent need for alternative treatments that are both
effective and carry fewer side effects. The Annonaceae
family, with its historical use in traditional medicine
across various cultures for treating inflammation and
pain, presents a promising avenue for research. Yet, the
potential of these plants to offer safer, natural
alternatives has not been fully explored or understood
within the scientific community.[7]
Therefore, the research was to conduct a thorough review
and analysis of the available scientific literature on the
Annonaceae family's anti-inflammatory and analgesic
constituents. This review aims to consolidate current
knowledge, identify research gaps, and suggest future
directions for exploring the Annonaceae family as a
source of new and safer anti-inflammatory and analgesic
drugs. Addressing this problem, the research seeks to
contribute to the fields of ethnopharmacology and drug
discovery, potentially being useful as a lead to the
development of novel treatments for patients suffering
from inflammation and pain.[8]
The exploration of Annonaceae species for their
medicinal properties is fragmented, with research
scattered across different species, regions, and
methodologies. This lack of consolidated knowledge
hampers the ability of researchers and healthcare
professionals to fully understand and leverage the anti-
inflammatory and analgesic moieties of this plant family.
Preliminary studies suggest significant benefits, yet the
specific compounds responsible for these effects, their
mechanisms of action, and optimal dosages remain
poorly defined. Without a comprehensive review and
analysis of existing research, the development of
Annonaceae-based treatments remains a problem,
leaving a gap in the development of bioactive agents
against chronic pain and inflammation[9], hence the need
for this review to present at a glance, the established
antiinflammatory and analgesic constituents of the
Annonaceae family. This study aims to systematically
gather and evaluate the existing literature on the anti-
inflammatory and analgesic constituents of Annonaceae
species.
METHODOLOGY
The information presented in this review was gathered
through comprehensive search of academic research
databases, peer-reviewed journals, and search engines.
Searches of the Cochrane Library, Academia, PubMed,
ResearchGate, and Google Scholar databases were
performed using the keywords: Annonaceae,
inflammation, pain management, chronic pain, analgesia,
chemistry of Annonaceae family, antiinflammatory
properties of Annonaceae, analgesic properties of
Annonaceae, mechanism of action, and phytochemical
constituents of Annonaceae.
Pharmacological activities and bioactive constituents
of the Annonaceae family
1. Annona muricata Linn.
The Fruits of A. muricata are used to prepare syrups,
canches, ice-creams and various beverages and have
traditional uses to treat cancer, bacterial and parasitic
infections and hypertension. Fruit is eaten as a natural
medicine for pain related diseases as arthritic pain,
arthritis and rheumatism. Leaves administered as a
decoction and drunk are used to treat headaches and
when applied topically, are used to treat abscesses and
rheumatism. Leaf-infusion has been used to treat
hypertension, heat and palpitation of the heart. Crushed
seeds have shown anthelmintic properties. Plant has also
been used to treat respiratory problems- bronchitis and
cough, pain and inflammation. Crushed leaves or
decoction may be taken orally to treat cancer and mouth-
wound infections.[10]
GC-MS analysis of A. muricata fruits revealed the
presence of alkaloids- annonaine, nornuciferine,
asimilobine; annonaceous acetogenins- epomusenin A &
B, epomurinin A & B, cis-annoreticuin, muricin J, K and
L; and phenolics-5-caffeoylquinic acid, p-coumaric acid
and its methyl ester, dicaffeoylquinic acid,
feruloylglycoside, 4-feruloyl-5-caffeoylquinic acid.
Essential oil compounds of the A. muricata fresh fruit
pulp contained methyl 2-hexenoate, ethyl 2-hexenoate,
methyl 2-octenoate and methyl 2-butenoate as main
compounds. Additionally, α-caryophyllene, 1,8-cineole,
linalool, (R)-terpineol, linalyl propionate and calarene
were found in high concentrations.[11]
GC and GC-MS analysis of the leaf revealed acetogenins
annomuricin A, B, C and E, annomutacin, annohexocin,
muricapentocin, muricatocin A, B and C,
gigantetronenin, annonacin A, annopentocin A, B and C,
murihexocins A, B and C, annocatacin B, annocatalin,
muricoreacin; the alkaloids – annonaine, isolaureline,
xylopine, annonamine, (S)-norcorydine, (R)-4-O-
methylcoclaurine, (R)O, O- dimethylcoclaurine; the
flavonoids/phenols- Quercetin 3-O-α-rhamnosyl-(1→6)-
β-D- sophoroside, daidzein, argentinine, fisetin,
Enema et al. European Journal of Pharmaceutical and Medical Research
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genistein, morin, myricetin, robinetin, vitexin, gallic
acid, epicatechin, quercetin 3-O-rutinoside, quercetin 3-
O-neohispredoside, quercetin 3-O-robinoside, catechin,
chlorogenic acid, kaempferol 3-O-rutinoside, quercetin
3- O-glucoside, quercetin, kaempferol; and the
megastigmanes- annoionol A, B & C; annoionoisides,
vomifoliol, roseoside, citroside A, blumenol C, loliolide,
(Z)-3-hexenyl β-D-glucopyranoside, anthraquinones,
vitamins, essential oil and carotenes. The essential oil
constituents were α-pinene, β-pinene, ρ-mentha-2,4(8)-
diene, β-elemene and germacrene D. The leaf essential
oil constituents were β-caryophyllene, δ-cadinene, epi-α-
cadinol and α-cadinol. Composition of essential oils was
noted by different researchers from different locations.
Roots contain acetogenins- montecristin, cohibin A & B,
cis solanin, cis-panatellin, cis-uvariamicin I & IV, cis-
reticulatacin, chatenaytrienin 1-3, muridienin 3 & 4,
coronin, sabadelin, muricadienin while the seeds contain
murisolin, muricatacin, corossolone, annonacin,
corrossolin, solamin, isoannonacin, gigantetrocin B,
muricatetrocin A & B, annocatacin A, arianacin,
javoricin, cis-annonacin-10-one, longifolicin, muricin A-
I, and the alkaloids reticuline, coclaurine, coreximine,
atherospermine, stepharine, anomurine and
anomuricine.[12]
The fruit pulp was reported to contain the alkaloids
reticuline, N-Methylcoclaurine; the acetogenins
montecristin, epomurinins A & B, sabadelin, annonacin,
corrossoline and muricenin; flavonoids and phenolic
acids- dicaffeoylquinic acid, coumaric acid, kaempferol,
luteolin and glycosides, morin, myricetin; vitamins and
carotenoids- α and β carotenes, vitamin C, lutein,
lycopene, cryptoxanthin β, α and γ- tocopherols. Over
120 acetogenins were reported to occur as part of the 212
compounds reported in A. muricata using GC-MS
studies.[13]
OOH
OH O
OH
OHOH
O
(H2C)11
CH3
O
Me
O
O
OH
OH
OH
Annohexocin Isoannonacin
NH
OH
OH
CH3O
Coclaurine
O
(H2C)11
CH3
OH
OH
OH
O
Me
O
OH
OH
Muricatocin A
NH
O
CH3
O
O
CH3
CH3
OH
N
O
O
H
CH3
OCH3
OH
CH3
Anomuricine (6,7-Dimethoxy-1{4,methoxy phenyl} Reticuline methyl-1,2,3,4-
tetrahydroisoquinolin-5-ol
Figure 1: Chemical structures of compounds from A. muricata.
Enema et al. European Journal of Pharmaceutical and Medical Research
www.ejpmr.com │ Vol 11, Issue 7, 2024. │ ISO 9001:2015 Certified Journal │
44
The plant A. muricata has demonstrated anticancer,
antimicrobial, anti-ulceric, wound-healing, antioxidant,
antiprotozoan, insecticidal, larvicidal, cytotoxic, anti-
arthritic, anti-parasitic, anticonvulsant, antimalarial,
antidiabetic and hepato-protective activities. In addition,
plant has shown anti- inflammatory, sedative, smooth
muscle relaxant, hypotensive, analgesic and
antispasmodic effects. Seed acetogenin constituents-
Muricin A-I were reported to show toxicity against
human hepatoma cells and toxicity against lung, breast
and colon cancer cells. The leaf acetogenins also showed
toxicity against human hepatoma cells as well as lung,
colon, pancreatic cancer cells. The fruit acetogenins,
muricin J, K and L showed toxicity against prostate PC-3
cancer cells. Leaf extract was found toxic against
chloroquine sensitive and resistant strains of P.
falciparum thus confirming anti-plasmodial activity.[14]
2. Annona reticulata Linn
The stem bark of A. reticulata is astringent and its extract
is taken as tonic. Decoction of stem bark or dried or
pulverized unripe fruit is administered in dysentery and
diarrhea. Leaves administered as tea drink or decoction
relieves colic, malaria symptoms, syphilis while crushed
leaves or paste are used topically as poultice for
abscesses and ulcers. Root decoction is taken for fever
and epilepsy while root bark extract is used against
toothache.[15]
Chromatographic techniques on A. reticulata seeds
resulted in discovering a new gamma-lactone acetogenin,
named cis-/trans-isomurisolenin, and the identification of
six other known cytotoxic acetogenins: annoreticuin,
annoreticuin-9-one, bullatacin, squamocin, cis-/trans-
bullatacinone, and cis-/trans-murisolinone. The structural
identification of these substances was achieved through
mass spectrometry and other spectral analysis
techniques. Among these compounds, several exhibited
significant cytotoxic effects on four types of cancer cell
lines: Hep 2,2,15, Hep G2, KB, and CCM2.[16]
The leaf essential oil of A. reticulata contains
sesquiterpenes and aromatic esters containing (Ε, Ε)-
farnesyl acetates, ar-turmerone, benzyl benzoate and γ-
terpinene as major constituents. Leaf exracts gave
annonaretin A, kaurenoic acid, taraxerol, β-sitosterol,
16α-hydro-19-al-ent-kauran-17-oic acid, 6β-
hydroxystigmast-4-en-3-one, 17-acetoxy-16β-ent-19-oic
acid, 16α-hydro-ent-kauran-17, 19-dioic acid and (2S)-
di-O-methylquiritigenin. Significant variations were
observed in the compositions of essential oils from the
fruits and leaves of all Annona species studied, but α-
pinene, camphene, β-myrcene, α-copaene, β-elemene, β-
caryophyllene, germacrene D, δ-cadinene, spathulenol
and caryophyllene oxide seem to be common to all
species. The root oil was found to be rich in spathulenol,
δ-cadinene, α-muurolene, β-bisabolene and α-
bergamotene.[17]
CH3OO
O
OH
OH
O
OH
Rolliniastatin-2
O
O
O
CH3
OOH OH OH CH3
6
6
Bullatacin
CO2H
CH3
CH3R
CH3
CH3CO2H
OAc
R=CHO, 16α-hydro-19-al-ent-kauran-17-oic acid 17-acetoxy-16β-ent-kauran-19-oic acid
R=CO2H, 16α-hydro-ent-kauran-17, 19-dioc acid
CH3O
O
O
OH
CH3
OH
H
O
H
H
H
OH
O
OCH3
O
H3CO
Molvizarin (2S)-Di-O-methylquiritigenin
Figure 2: Chemical structures of compounds from Annona reticulata Linn.
Enema et al. European Journal of Pharmaceutical and Medical Research
www.ejpmr.com │ Vol 11, Issue 7, 2024. │ ISO 9001:2015 Certified Journal │
45
The plant has shown anti-inflammatory, anti-malarial
and analgesic activities. Annonaceous acetogenins are
well known for their anti-inflammatory activities and
solamin, annoreticulin-9-one, annomonicin, squamone
and rolliniastatin have shown this activity.[18]
3. Annona glabra Linn.
A. glabra is used in traditional medicine as an anti-
inflammatory and anticancer drug. Leaves and leafy
shoots are used in the preparation of cough mixture. The
fruit has an edible yellow pulp. The plant contains an
essential oil with several biological activities such as
analgesic and anti-inflammatory activities. Terpenes
present in the fruit can be used in cosmetics and
pharmaceuticals for the production of useful
products.[19][20]
GC-MS study of A. glabra gave acetogenins, ent-
kaurenes, peptides and alkaloids. Fresh fruits and stem
gave annoglabasin G (16α-hydro- 19-acetoxy-ent-
kauren-17-al), Plant gave 18 kaurene diterpenoids-
including 16β-hydro-ent-kauren-17-oic acid, 16α-hydro-
ent-kauren-17-oic acid, 19-nor-ent-kauren-4α-ol-17-oic
acid, 16α-hydro 19-ol-ent-kauren-17-oic acid ent-kaur-
16-en-19-oic acid, 16α-hydroxy-ent-kauran-190oic acid,
16α, 17-dihydro-ent-kauran-19-oic acid, 16β, 17-
dihydro-ent-kauran-19-oic acid, 16α-hydro-ent-kauran-
17, 19-dioic acid, 16β-hydroxy-17-acetoxy-ent-kauran-
19-oic acid; four acetogenins- annomontacin, annonacin,
isoannonacinine and squamocin; 5 steroids including β-
sitosterol, stigmasterol, β-sitosteryl-D-glucoside,
stigmasteryl-D-glucoside, 6-O-palmitoyl-β-sitosteryl -D-
glucoside; 2 oxoaporphines- liriodenine and lysicamine;
1 dioxoaporphine- annobraine (lettowianthine); 5
aporphines- (-)-nor nuciferine, (-)- annonaine, (-)-N-
formylanonaine, (-)-asimilobine and (+)- nordomesticine;
1 proaporphine identified as (+)-stepharine; 2
protoberberines- (-)-kikemanine, dehydrocorydalmine; 1
azaanthraquinone- 1-aza-4-methyl-2-oxo-1, 2- dihydro-9,
10-anthracenedione and 2 amides- N-trans-
feruloyltyramine and N-p-coumaroyltyramine. Other
compounds are dihydrophaseic acid 1, 3’-di-O-β-D-
glucopyranoside, icariside D2, icariside D2 6’-O-β-D-
xylopyranoside, 3, 4-dimethoxyphenyl -O- β-D-
glucopyranoside, 3, 4- dihydroxybenzoic acid, blumenol
A, cucumegastigmane 1 and icariside B1. The main
compounds of Annona glabra were β-caryophyllene,
germacrene D, α-cadinol and β-elemene. In another
study, the most abundant compounds were terpenoids,
principally α-pinene, limonene, α-phellandrene and (E)-
β-ocimene. The concentrations and compounds found
sometimes vary according to many factors-season,
location, stage of maturity of leaves or fruits etc.[21]
CH3
CH3
OH
OH
CH3CH3
O
Blumenol A
O
O
OH
OH
OH
OH OH
β
R=H, Icariside D2
R=Xylopyranosyl, Icariside D2-6-O-β-D-xylopyranoside
C
H
O
CH3
CH3
OH
O
CH3CH3
O
OH
OH
OH
OH
OOCH3
OCH3
O
OH
OH
OH
OH
Icariside B1 3,4-DimethoxyphenylO-β-D-glucopyranoside
N
O
O
H
H
N
OH
O
CH3
H
H
N
O
O
O
O
Asimilobine Annonaine Annobraine (Lettowianthine)
Figure 3: Isolated compounds from Annona glabra Linn.
Enema et al. European Journal of Pharmaceutical and Medical Research
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46
4. Annona senegalensis Persoon
Traditionally, A. senegalensis is used as a stimulant and
pain reliever. Extracts of the plant are used to treat
swelling around the eyes, aches and pains- toothache,
headache, malaria and mouth infection. All parts of A.
senegalensis contain varying amounts of essential oils.
GC-MS analysis of the volatile components of fruit or
leaf oil include car-3-ene, linalool, citronellal, thymol,
citronellol, geranial, 1,2-benzene diol, butylated
hydroxytoluene and derivatives, fatty acids-
hexadecanoate, oleic acid, 13-octadecadien-1-ol,
octadecanoic acid, 9,17-octadecadienal; alkanes-
hexadecane, tetracosane, heneicosane, pentadecane,
tetratriacontane and squalene. The essential oil of air-
dried leaves contained germacrene D, β-caryophyllene,
γ-cadinene and α-humulene. Other isolates include the
diterpenoids- kaur-16-en-19-oic, kaurenoic acid,
cavacrol, 1-dodecanol, kaur-160en-18-oic acid and β-
caryophyllene. Cyclopeptides isolated from the seeds
were cyclosenegalen A & B and glabrin A which are also
constituents of other Annona species. Annogalene,
annosenegalin, acetogenins, kaurenoic acid and
derivatives and the alkaloid (-)-roemerine are the major
bioactive constituents of A. senegalensis. Annona
senegalensis demonstrated antimalarial, analgesic, anti-
inflammatory for the root extract while leaf extracts
showed strong anti-inflammatory and trypanocidal
properties.[18]
N
O
O
HCH3
H
CH3
OH
O
H
CH3
O
(-)-Roemerine
Kaurenoic acid
Figure 4: Chemical structures of compounds from
Annona senegalensis Persoon.
5. Annona squamosa Linn.
The leaves of A. squamosa are used as a vermifuge and
for treating cancerous tumours in traditional medicine. It
is also applied as a paste or lotion to abscesses, insect
bites and other skin problems. The leaves have also been
used as insecticide, anthelmintic and styptic. Stem bark
is used as a powerful astringent, anti-dysenteric and
vermifuge. Root- bark scrapings or decoction are used
for toothache and whole root is purgative. Powdered seed
is used to kill fleas and headlice and is believed to have
antifertility/abortifacient activity.[22]
Isolation and characterization of the seeds of A.
squamosa yielded amino-acids, mono and
sesquiterpenes, kaurenes, acetogenins and alkaloids
including annonaine. Seeds furnished acetogenins-
squamostanal A, squamosin- O1 and O2, squamosatin-A,
squamocins B to N and three lignans consisting of
coumarin moiety- cleomiscosin A, B and C. Other
isolated compounds were liriodenine, oxoanalobine,
duguevalline, roemeolidine and N, Nitrosoxylopine. Leaf
oil components were β-cedrene, β-caryophyllene,
germancrene D, β-elemene and β-pinene.[12]
N
O
O
N
O
O
O
OH
O
O
O
R1
OH
OCH3
CH3
O
CH2OH
Liriodenine Oxoanalobine R=H, Cleomiscosin A
R=CH3, Cleomiscosin C
N
O
ONO
OCH3
N
OH
OH
O
CH3
N
OCH3
O
O
H3CO
N-Nitrosoxylopine Roemerolidine Diguevalline
Figure 5. Chemical structures of compounds from Annona squamosa Linn.
The isolated aporphine alkaloids-N-Nitrosoxylopine,
roemerolidine and duguevalline demonstrated in vitro
anti-inflammatory activity. A. squamosa extracts
displayed anti-inflammatory and analgesic activities.
Annona essential oils possess several biological activities
Enema et al. European Journal of Pharmaceutical and Medical Research
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47
such as anticancer, analgesic and anti-inflammatory
properties.
6. Artabotrys
Plants of the Artabotrys genus have been used over the
years traditionally for the treatment of malaria, diarrhea,
backache, and inflammations.[23] Genus Artabotrys
belongs to the custard apple family Annonaceae (the
subfamily Annonoideae, the tribe Unoneae), including
over one hundred species of small shrubs and woody
climbers.[24] The plants of this genus are native to
tropical and subtropical areas, especially highly
concentrated in Africa and Eastern Asia. Traditional
uses of Artabotrys species included treating a variety of
illnesses, such as cholera, scrofula, and malaria.[25]
Compounds such as Anonaine, isolated from A.
odoratissimus and A. aurantiacus, exhibit anti-
inflammatory and anti-malarial properties while others,
like Artabonatine F from A. uncinatus roots, showed
analgesic activity. Atherospermidine, found in several
Artabotrys species, also shows anti-inflammatory and
anti-malarial effects. Compounds like Aurantiacine A
and (+)-Flavinantine from A. aurantiacus liana are noted
for their antiplasmodial properties. Additionally,
compounds such as Artaboterpenoid A from A.
hexapetalus stem and Artabotryol A from A.
odoratissimus seeds are highlighted for their anti-
inflammatory and anti-malarial activities.[26]
N
O
O
R R1
R2
R3
R4
N
O
OR
O
R=R1=R2=R3=R4=H: Anonaine
R=OMe, R1=R2=R3=R4=H: (-)-norstephalagine
R=OMe: Atherospermidine
R=H: Artabonatine A
N
MeO
R
R1
R2
R3
O
R=R1= H, R2=R3= OMe: Artabonatine C
R=R1= H, R2= OMe, R3= OH: Artabonatine D
Figure 6: Chemical structures of compounds from Artabotrys.
7. Enantia chlorantha Oliv.
E. chlorantha is a multipurpose medicinal plant and used
traditionally for the treatment of pains, malaria as well as
inflammations. The stem bark is furnished with
Osupupine, an isoquinoline alkaloid identified as 1-
(3’,4’-dimethoxy-2’-hydroxybenzylidene)-1,2,3,4-
tetrahydro-6,7-dimethoxy-n-formylisoquinoline. The
stem bark also furnished protoberberine alkaloids,
berberine, palmatine (berbericinine), columbamine and
jatrorrhizine. 7,8-Dihydro-8-hydroxy palmatine and
palmatine were reported from an extract of the stem bark
that was found to have anti-HIV activity. The root bark,
in addition, gave 2 oxyaporphines-O-methyl
moschatoline and lysicamine. The leaf gave flavonic
heterosides, phenanthrine alkaloids and the alkaloids
atherospermine and argentinine.[27]
N+
OCH3
OCH3
R2O
R1O
X
-
R1 = H ; R2 = CH3, Jatrorrhizine
R1 = CH3 ; R2 = H, Columbamine
N+
O
O
OCH3
OCH3
X
-
Berberine
N+
O Me
O Me
Me O
Me O
Palmatine
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N
O Me
O Me
Me O
Me O OH
7,8-Dihydro-8-hydroxy palmatine
Figure 7: Chemical structures of compounds from Enantia chlorantha Oliv.
Stem bark extract showed anti-inflammatory properties.
It was shown that an aqueous extract of the plant was
able to repair or reverse the liver damage produced in
experimental rabbits. Protoberberines isolated from stem
bark synergistically had preventive and curative effects
on artificially-provoked liver injury. Berberine
demonstrated anti-inflammatory and anti-malarial
properties. It was confirmed that aqueous extract of plant
possess potent anti-malarial activities comparable to that
of chloroquine and may be ascribed to the significant
presence of alkaloids and phenolics. Osupupine was
highly active against chloroquine-resistant Plasmodium
falciparum.[28]
8. Dennettia tripetala Barker F.
D. tripetala fruit has a peppery spicy taste and is used
traditionally as a remedy for fevers, cough, toothache,
nausea etc. and the fruits are commonly eaten as spice or
stimulant. Young leaves and fruits have a distinctive
spicy taste and have been chewed or eaten as appetite
stimulant and for the relief of cough. The various parts,
in combination with other plant parts are used to treat
infantile convulsions, typhoid, worm infestation and
vomiting.[29]
Chemical compounds such as dennetine (2, 6-
dimethoxychromone), 3-phenanthrene alkaloids-
uvariopsine, stephenanthrine, argentinine and vanillin
have been isolated from the roots; GC-MS analysis of the
fruit essential oil gave 2-phenylnitroethane (72.41%),
linalool (18.0%) and (6E) – nerolidod (4.51%), o-
cymene, β-ocimene, copaene, -farnescene,
caryophyllene and its oxide, eudesmol. D. tripetala fruit
essential oils contain 1-nitro-pentane, α- and β-cinene,
camphene, β-myrcene, α-phellandrene, p-cymene, (+)-4-
carene, β-ocimene, linalool, α-terpinene, phenylethyl-
alcohol, borneol, terpin-4-ol, α-terpineol, safrole, 2-
methylphenyl formate, elemene, caryophyllene,
humulene, α-farnescene, caryophyllene oxide, copaene,
4-epi-cubenol, guaiol, α-eudesmol, trans-cadinol, azulen-
5-ol, ascorbic acid 2,6-dihexadecanoate and 9-
octadecenoic acid. Leaf fatty acid composition, caprylic,
capric, lauric, myristic (tetradecanoic), myristoleic
(Tetradec-9-enoic), palmitic, palmitoleic (hexadec-9-
enoic), stearic, oleic (cis-9-Octadecenoic), linoleic (Cis,
cis-9, 12-octadecadienoic), linolenic (cis, cis-9,12,15-
octadecatrienoic) acid.[30]
NCH3
CH3O
OH
CH3
CH3
O
O
OCH3
CH3
CH3
OH CH3
Argentinine 2-methylphenyl) methyl Formic acid ester
CH3
O
CH3
OH
CH3
O
OCH3
N
CH3
O
OCH3
OCH3
CH3
NOO +
Linalool Stephenathrine Uvariopsine 2- Phenyl nitroethane
Figure 8: Chemical structures of compounds from Dennetia tripetala Barker F.
9. Xylopia aethiopica (Dunal) A.Rich.
X. aethiopica (Dunal) A.Rich. (Annonaceae). The plant
is commonly known as “spice tree,” “Africa pepper,”
“Ethiopian pepper,” or “Guinea pepper.” The fruits are
reported to have high nutritive and medicinal values
including being used for the treatment of pain. Several
scientific studies have confirmed the traditional use of X.
aethiopica against pain and inflammation.[31] found that
the antiinflammatory actions of the ethanolic extract of
the 70% aqueous ethanol extract of the fruits of X.
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aethiopica are exerted through the inhibition of
histamine release from mast cells. The extract (30–
300 mg/kg) was inhibited by 23–62% mouse pinnal
inflammation. The analgesic and anti-inflammatory
properties of the methanol extract of X. aethiopica have
been investigated by the acetic acid–induced pain
(writhing) model in mice and carrageenan-induced
inflammation in rats as a model of acute
inflammation.[32] Also, the ethanol extract of X.
aethiopica and its major diterpene, xylopic acid,
inhibited acetic acid–induced visceral nociception,
formalin-induced paw pain (both neurogenic and
inflammatory), and thermal pain as well as carrageenan-
induced mechanical and thermal hyperalgesia in murine
models.[33]
GC-MS analysis of the Fruit revealed kaurene
diterpenes-xylopic acid, xylopioxyde, kaur-15-ene, 13-
epimanoyloxide, ent-kaur -16- en-19-oic acid and 15-
oxo-ent-kaur-16-en-19-oic acid; terpenes and
derivatives- and β-pinene, 1,8-cineole, o-cymene,
pinocarveol, α-terpineol, myrtenol, cumic alcohol,
elemol, (+)-spathulenol, cis- -copaene-8-ol, and fatty
acid-hexadecanoic acid methylester.[34] Trunk bark
constituents were also analyzed along with root bark and
fresh and dried fruits. The major constituents were
monoterpene hydrocarbons with β-pinene as major
component; trans-m-mentha-(7), 8-diene was the main
compound in the essential oils of the leaves and the barks
of roots and stems.[35]
CH2
CH3
CH3COOH
CH2
O
CH3
CH3COOH
CH2
CH3
CH3COOH
OCOCH 3
ent-kaur-16-en-19-oic acid 15-oxo-ent-kaur-16-en-19-oic Xylopic acid,
15α-acetoxy-ent-kaur-16-en-19-oic acid
CH3COOH
CH3
O
O
Xylopioxyde
Figure 9: Chemical structures of compounds from Xylopia aethiopica (Dunal) A.Rich.
The essential oil showed strong antibacterial, antioxidant
and antifungal effects making the fruit useful in the
treatment of diseases caused by microbes and fungi. X.
aethiopica extracts showed anti-anaphylactic, analgesic
and anti-inflammatory actions in mice, while the seeds
have shown carminative, analgesic and restorative
properties.
10. Monodora myristica (Gaertn.) Dunal
The seeds of M. myristica are useful as a seasoning
because of its aromatic flavor; the kernel is a well-known
condiment used as a spice in both African and
Continental dishes. The ground seed, prepared as a soup
is a stimulant to relieve constipation; it has shown
diuretic properties, it is antiseptic and is valuable in
treating mild fever. Various communities have used the
seeds and its essential oil constituents in the treatment of
headache and hypertension. Stem bark extract is used to
treat stomachache, haemorrhoids, rheumatism and febrile
pains. The seeds are aromatic and are traded for their
economic values in use as condiment. The powdered
seeds extracts have been used, taken internally to treat
stomach complaints and relieve constipation and
sprinkled on sores for healing. The oil in various parts
have proven beneficial.[36]
Seeds, the most useful part of the plant contain 5-9% of
essential oil and about 35-36% of a red-brown fixed oil
containing linoleic acid (46.9%) and oleic acid (35%) as
major constituents. Flavonoid compounds found in the
seed are-catechin, daidzein, genistein, apigenin,
naringenin and its chalcone derivative, kaempferol,
luteolin, epicatechin, myricetin, isorhamnetin, quercetin,
rutin, 4-O-methyl epicatechin and epigallocatechin-3-O-
gallate; phenol and its derivatives are phenylacetic acid,
salicylic acid, cinnamic acid, protocatechuic acid,
gentisic acid, p-coumaric acid, vanillic acid, safrole,
eugenol and its isomer and its methyl derivatives-methyl
eugenol and methyl isoeugenol, gallic acid, caffeic acid,
ferulic acid, syringic acid, piperic acid, sinapic acid,
shogaol, 3-O-caffeoyquinic acid, chlorogenic acid,
rosmarinic acid and Phenyl-6-O-malonyl-β-D-glucoside.
Terpene derivatives include myrcene, carvacrol,
elemicin, myristicin and other constituents- gingerol,
coumestrol, glycitein, capsaicin, curcumin, miquelianin,
eriocitrin, gallocatechin derivatives, papain and lupeol.
Seed essential oil constituents were linalool (15.10%), δ-
cadinene (11.09%), germacrene-D-4-ol (25.48%) and
traces of γ-terpinene, trans-p-menth-2-en-1-ol, α-
terpineol, p-thymol, caryophyllene, γ-muurolene, β-
patchoulene and α-cadinol. The plant growing in
Cameroon contains seeds with α-phellandrene, α-pinene,
myrcene, limonene and pinene. The stem bark oil
constituents were α-cubebene, caryophyllene, α-
farnescene, γ-muurolene, α-elemene (17.98%), γ-
cadinene (31.31%), acoradiene, cis-nerolidol (7.62%)
and traces of guaiol, cadinadiene, copaene and α-
bisabolol. Leaf essential oil contains β-caryophyllene, α-
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humulene and α-pinene. These compounds were identified through GC-MS analysis.[36]
OH
COOH
CH2
O
CH3
OCH3
COOH
OH
OH
HO
OHO
OH O
OH
Salicylic acid
Methyl eugenol
Gallic acid
Naringenin
OHO
OH O
OH
OH
OCH3
OH
OH
CH2CH COOH
O
CO CH CH
OH
OH
Isorhamnetin
Rosmarinic acid
Figure 10: Chemical structures of compounds from Monodora myristica (Gaertn.) Dunal.
The Plant is antiseptic, anti-inflammatory, anti-oxidant,
hypotensive and antisickling and was found to lower
cholesterol and modulate lipid peroxidation in laboratory
animals. Monodora myristica was found to ameliorate
antioxidant levels as well as serum AST and ALT
activities, just as the seed flavonoid-rich fraction
ameliorated carbon tetrachloride-induced hepatotoxicity
and oxidative stress in rats, and the root bark extract
ameliorated acute and chronic inflammation. Aqueous
extracts could reverse liver toxicity induced by high
cholesterol diets and exert hypocholesterolemic effect.[37]
11. Monodora tenuifolia Benth
The stem bark and root extracts are used to treat
toothache (use as chew stick). The edible fruits provide
an aromatic seed which are traded and used as
condiment. The powdered seeds are used in various
forms for treating malaria. Chemical compounds
identified from M. tenuifolia seeds include the
flavonoids-catechin, daidzein, genistein, apigenin,
naringenin and its chalcone derivative, kaempferol,
luteolin, epicatechin, myricetin, isorhamnetin, quercetin,
rutin, 4-O-methyl epecatechin and epigallocatechin-3-O-
gallate; phenol and derivatives-phenol, phenylacetic acid,
salicylic acid, cinnamic acid, protocatechuic acid,
gentisic acid, p-coumaric acid, vanillic acid, safrole,
eugenol and its isomer and methyl derivatives-methyl
eugenol and methyl isoeugenol, gallic acid, caffeic acid,
ferulic acid, syringic acid, piperic acid, sinapic acid,
shogaol, 3-O-caffeoyquinic acid, chlorogenic acid,
rosmarinic acid and Phenyl-6-O-malonyl-β-D-glucoside.
Terpene derivatives include myrcene, carvacrol,
elemicin, myristicin and other constituents- gingerol,
coumestrol, glycitein, capsaicin, curcumin, miquelianin,
eriocitrin, papain, lupeol, dimethylallylindole and 6-(3-
Methylbuta-1,3-dienyl) indole. These were identified
using GC-MS analysis.[38]
O
OH
OH
OH
HO
OH
CH3
O
O
CH3
CH3
O
O
O
CH2
CH3
CH3
CH3
Catechin
Methyl Isoeugenol
Elemicin
O
OH
R O
HO
O
OCH2
R = H; Daidzein
R = Genistein
Safrole
Figure 11: Chemical structures of compounds from Monodora tenuifolia Benth.
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12. Uvaria chamae P. Beauv.
The plant U. chamae is used traditionally in the
treatment of fevers. Whole fruit macerate is taken orally
for malaria.[39]
In a typical herbal formula, the roots of U. chamae and
Hippocratea pallens Planch (Celastraceae) are chopped
and boiled in water. The extract is allowed to cool. This
is strained and drunk in regular doses as appropriate to
manage urinary problems, particularly urine retention.
This medication is indicated also for nose bleeding,
epilepsy, typhoid & yellow fever, jaundice and pile. In
the same way a decoction of U. chamae root,
Entandrophragma utile (Cedar) stem bark and Cyperus
esculentus root and seed may be taken at regulated doses
to treat infertility and impotence and associated health
problems. The flavonoids in U. chamae are pinocembrin,
pinostrobin, chamanetin 5-methylether, isochamanetin,
dichamanetin-5-methyether, diuvaretin, chamuvaritin,
uvarinol, chamanetin, isouvaretin, uvaretin,
dichamanetin, chamuvarinin. GC-MS analysis of the
essential oil revealed C-benzylated monoterpene
chamanen, benzyl benzoates and
thymoquinoldimethylether. A sample of U. chamae
growing in Badagry, Nigeria afforded an essential oil
with I-Nitro-2-phenylethane (63.2%), linalool (9.9%)
and germancrene D (6.6%) as major constituents.[40]
O
OR3O
R2
HO
R1
O
OH O
RO
O
O R2
R1
benzoate
R=H, Pinocembrin;
R=CH3 =pinostrobin
R1=H,R2=OCH3,Omethoxybenzybenzoate
R1 = R2 = H, Benzyl
CH2
HO
R
1
=
CH2
HO
R
1
=
R2 =R3=H, Chamanetin
R2= H, R3=CH3, Chamanetin 5-methyl ether
OOO
CH3
CH3
O
CH3
OH
O
(+)- chamuvarinin
Figure 12: Chemical structures of compounds from Uvaria chamae P. Beauv.
13. Duguetia lanceolata A.St.-Hil.
Many species of Annonaceae have been used to treat
inflammatory diseases in folk medicine. Pharmacological
studies have shown that some terpenoids and essential
oils from this family have significant anti-inflammatory
effects, such as caryophyllene oxide and the essential oil
of D. lanceolata. The essential oil from the branches
of D. lanceolata, which is rich in β-elemene (8.3%), β-
caryophyllene (6.2%), caryophyllene oxide (7.7%), β-
eudesmol (7.2%), β-selinene (7.1%), and δ-cadinene
(5.5%), played a crucial role as a protective factor
against carrageenan-induced acute inflammation.[41]
GC-MS analysis of essential oil from the bark of the
underground stem of Duguetia furfuracea, revealed (E)-
asarone (21.9%), bicyclogermacrene (16.7%), 2,4,5-
trimethoxystyrene (16.1%), α-gurjunene (15.0%), and
cyperene (7.8%), was shown to have anti-inflammatory
effects.[42]
14. Saccopetalum tomentosum (Roxb.) Hook.f. &
Thomson
The leaf extract of S. tomentosum showed anti-
inflammatory activities and sub-acute toxicity of hydro-
ethanolic. Results of anti-inflammatory has shown that
the tested extract 200mg/kg was found more active with
the inhibition percent of oedema by the tested extracts at
2 dose level 100mg/kg and 200mg/kg using the formalin-
induced rat paw oedema model using diclofenac sodium
as the reference drug.[43]
Antiinflammatory Constituents of the Annonaceae
Family
The family Annonaceae, known for its diverse genera
and species, has been extensively studied for its rich
content of bioactive compounds with anti-inflammatory
and analgesic properties. Annona glabra stands out with
its notable anti-inflammatory compounds such as
annonaceous acetogenins, annomontacin, annonacin,
isoannonacinine, squamocin, and annoreticulin-9-one. Its
analgesic properties are also attributed to essential oils
containing terpenes, β-caryophyllene, germacrene D, α-
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cadinol, and β-elemene. These compounds have been
isolated and their efficacy documented in various
pharmacological studies, emphasizing their potential in
managing inflammatory and pain-related conditions.[44]
Another species, Annona reticulata, has been reported to
contain anti-inflammatory compounds such as
annoreticuin, annoreticuin-9-one, bullatacin, squamocin,
cis-/trans-bullatacinone, and cis-/trans-murisolinone. Its
analgesic properties are linked to sesquiterpenes and
aromatic esters, including (Ε Ε)-farnesyl acetates, ar-
turmerone, benzyl benzoate, and γ-terpinene. Studies on
these compounds have highlighted their ability to inhibit
key inflammatory pathways and provide relief from pain,
supporting their traditional use in folk medicine.
Annona senegalensis also contributes significantly to the
Annonaceae family's medicinal profile. It contains anti-
inflammatory compounds such as germacrene D, β-
caryophyllene, γ-cadinene, α-humulene, kaur-16-en-19-
oic acid, kaurenoic acid, annogalene, annosenegalin, and
acetogenins. Essential oils derived from its leaves and
fruit further support the analgesic potential. Research has
demonstrated that these compounds exhibit strong anti-
inflammatory and analgesic effects, making them
valuable candidates for further drug development and
therapeutic applications.[45][46]
Annona squamosa has been identified to contain anti-
inflammatory compounds like squamostanal A,
squamosin-O1 and O2, squamosatin-A, squamocins B to
N, cleomiscosin A, B, and C, liriodenine, oxoanalobine,
duguevalline, and roemeolidine. Its analgesic properties
are attributed to β-caryophyllene, germacrene D, β-
elemene, and β-pinene. These compounds have
effectively reduced inflammation and alleviate pain in
various experimental models.[47] The studies and
references on these bioactive compounds underline their
significance and validate the traditional medicinal uses of
these species within the Annonaceae family.
CONCLUSION
Alkaloids such as annonaine, reticuline, and
atherospermidine have been identified across various
species, demonstrating significant bioactivities, including
anti-inflammatory and analgesic effects. Annonaceous
acetogenins, a unique class of compounds to the
Annonaceae family, have shown potent cytotoxic
activities against various cancer cell lines and also
exhibit anti-inflammatory properties. Terpenes and
essential oils containing compounds like β-caryophyllene
and germacrene D were prevalent across the species
studied, contributing to the anti-inflammatory and
analgesic activities. Flavonoids and phenolic acids,
known for their antioxidant properties, further support
the anti-inflammatory potential of Annonaceae species.
These findings highlight the potential for the
development of novel anti-inflammatory and analgesic
agents derived from natural products. The diversity of
chemical compounds identified suggests multiple
mechanisms of action could be exploited in the
development of new therapeutic agents. The evident
biological activities of these compounds, particularly the
anti-inflammatory and analgesic effects, underscore the
importance of further pharmacological studies to fully
understand their potential in drug development.
Moreover, the adverse effects associated with
conventional anti-inflammatory drugs, such as NSAIDs
and corticosteroids, necessitate the search for alternative
therapies with fewer side effects. The Annonaceae
family, with its diverse pharmacological properties,
offers a promising reservoir of compounds for
developing safer and more effective therapeutic agents.
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