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Review Article
Current Insights on Bioactive Molecules, Antioxidant, Anti-
Inflammatory, and Other Pharmacological Activities of
Cinnamomum camphora Linn
Mohamed Joonus Aynul Fazmiya ,
1
Arshiya Sultana ,
1
Khaleequr Rahman ,
2
Md Belal Bin Heyat ,
3
Sumbul ,
1
Faijan Akhtar ,
4
Salabat Khan ,
3
and Seth Christopher Yaw Appiah
5
1
Department of Amraze Niswan wa Ilmul Qabalat, National Institute of Unani Medicine, Ministry of Ayush, Bengaluru,
Karnataka, India
2
Department of Ilmul Saidla, National Institute of Unani Medicine, Ministry of Ayush, Bengaluru, Karnataka, India
3
IoT Research Center, College of Computer Science and Software Engineering, Shenzhen University, Shenzhen,
Guangdong 518060, China
4
School of Computer Science and Engineering, University of Electronic Science and Engineering, Chengdu, China
5
Health and Social Care Research Group, Department of Sociology and Social Work, Kwame Nkrumah University of Science
and Technology, Kumasi, Ghana
Correspondence should be addressed to Mohamed Joonus Aynul Fazmiya; mjafazmiya@gmail.com,
Arshiya Sultana; drarshiya@yahoo.com, Md Belal Bin Heyat; belalheyat@gmail.com, Faijan Akhtar; faijanakhtar98@gmail.com,
and Seth Christopher Yaw Appiah; scyappiah@knust.edu.gh
Received 7 July 2022; Revised 26 August 2022; Accepted 22 September 2022; Published 7 October 2022
Academic Editor: Tarique Hussain
Copyright © 2022 Mohamed Joonus Aynul Fazmiya et al. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
C. camphora is a renowned traditional Unani medicinal herb and belongs to the family Lauraceae. It has therapeutic applications
in various ailments and prophylactic properties to prevent flu-like epidemic symptoms and COVID-19. This comprehensive
appraisal is to familiarize the reader with the traditional, broad applications of camphor both in Unani and modern medicine
and its effects on bioactive molecules. Electronic databases such as Web of Science, PubMed, Google Scholar, Scopus, and
Research Gate were searched for bioactive molecules, and preclinical/clinical research and including 59 research and review
papers up to 2022 were retrieved. Additionally, 21 classical Unani and English herbal pharmacopeia books with
ethnomedicinal properties and therapeutic applications were explored. Oxidative stress significantly impacts aging, obesity,
diabetes mellitus, depression, and neurodegenerative diseases. The polyphenolic bioactive compounds such as linalool, borneol,
and nerolidol of C. camphora have antioxidant activity and have the potential to remove free radicals. Its other major bioactive
molecules are camphor, cineole, limelol, safrole, limonene, alpha-pinene, and cineole with anti-inflammatory, antibacterial,
anxiolytic, analgesic, immunomodulatory, antihyperlipidemic, and many other pharmacological properties have been
established in vitro or in vivo preclinical research. Natural bioactive molecules and their mechanisms of action and
applications in diseases have been highlighted, with future prospects, gaps, and priorities that need to be addressed.
1. Introduction
The WHO stated that around 80% global population uses
different types of traditional medicine to treat many diseases
[1]. Traditional medicine is the knowledge, skills, and proce-
dures that indigenous peoples and other cultures have used
for a long time in order to preserve health and avoid illness
[2, 3]. One of the oldest forms of medicine is Unani medi-
cine, which originated in Greek [4] and is based on seven
essential factors responsible for the maintenance of health
Hindawi
Oxidative Medicine and Cellular Longevity
Volume 2022, Article ID 9354555, 23 pages
https://doi.org/10.1155/2022/9354555
and imbalance any one of them can lead to disease or even to
death. The great physicians, Avicenna and Galan, stated that
the primary elements contribute to the formation of things
in nature [5]. The intermixture of primary elements forms
temperament. The temperament indicates the state of equi-
librium to the number of elements and the ratio of the par-
ticular compound and different combination responses to its
specific nature. Hence, any changes in the quality or quantity
of humor alter the equilibrium and disturb the normal tem-
perament. Proper physiological functions are maintained by
the homeostasis of temperament. Simple temperamental
imbalances cause intrinsic power (immunity) to fight back
and maintain body normal levels. If the body’s tempera-
ment, functions are impaired owing to a change in humor,
diet therapy, pharmacotherapy, regimental therapy, or sur-
gery may be required, depending on the situation [5, 6].
Temperament (Mizaj) and humor, which is the principal
concept in this system and disturbances in the quality and
quantity of humor, cause numerous conditions. The four
main modes of therapy available in Unani medicine [7] are
regimental diet therapy, pharmacotherapy, and surgery.
Correction through pharmacotherapy and regimental ther-
apy helps to maintain homeostasis of the humor [4]. First-
degree drugs are safer, temperamental quality is less, and
second-degree drugs are also safe and have strong tempera-
mental quality but no toxic effect. Third-degree tempera-
mental medicine drugs are strong, the toxic effect may
manifest prominently, and fourth-degree drugs are exces-
sively strong and toxic. The drug is moderate (Mutadil)in
temperament; it has no toxic, no temperamental quality,
and the activity is only limited medicinal effect. Commonly,
cold temperamental drugs are suitable for hot temperamen-
tal individuals and may produce effects on cold tempera-
mental individuals in inappropriate doses. Cinnamomum
camphora (L.) is a traditional Unani medicinal plant with a
third-degree cold and dry temperament and hence useful
in hot temperamental individuals [8].
C. camphora (L.) is a renowned Unani medicinal herb
applied for several disease conditions in Unani as well as
other traditional medicines. Camphor is a terpene ketone
derived from C camphora wood or synthetically produced
from turpentine. White, yellow, brown, and blue camphor
oil are the four different fractions of camphor oil [9–11].
Camphor is obtained by distillation with water from the
wood of trees or plants and purified by sublimation, and it
occurs in translucent white crystals [12–14]. Since the
ancient era in the Unani traditional system of medicine, C.
camphora has been using its ethnomedicinal properties like
antiseptic, analgesic, and rubefacient properties. Camphor
has been use for very long time in various traditional systems
of medicine such as Ayurveda, Unani, Siddha, and Chinese.
It has been used in Unani medicine mainly in respiratory
disorders (Amrāz-i-Riyah), gastrointestinal (Amrāz-i-Me‘da
wa Am’a), integument disease (Amrāz-i-Jild), eye diseases
(Amrāz-i-Ayn), and nervine and cerebral disorders
(Amrāz-i- damaghi wa a’sabi) especially in hot conditions
for headache, strengthening senses and brain [15], bilious
diarrhea [8], inflammation of the liver [15], and useful in
bladder and kidney inflammation [16]. Furthermore, exter-
nally, it is used for various ailments such as eye diseases,
ear pain, joint, muscular pain, chest congestion, and head-
ache applications such as ear drops or gargling with or with-
out other suitable drugs [12, 15, 16]. An overdose may result
in systemic toxicity. Signs of intoxication include gastroin-
testinal pain, emesis, agitation, tremors, and convulsions,
which are followed by CNS depression marked by apnea
and coma [17]. Furthermore, it is an important ingredient
of Arq Ajeeb used as a prophylactic medicine for COVID-
19 as per AYUSH guidelines. This comprehensive appraisal
is to familiarize the reader towards the extensive, well recog-
nized, and broad applications of camphor both in Unani and
contemporary applications.
To collect information on C. camphora for its tempera-
ment (Mizaj), adverse effects (Mudir), corrective (Muslih),
substitute (Badal), ethnomedicinal properties (Afa’l), Unani
compound formulations, and ethnomedicinal therapeutic
uses, a literature survey of traditional Unani texts was con-
ducted. Additionally, full-text paper and thorough search
of electronic databases such as PubMed, Scopus, Google
Scholar, and Research Gate were conducted to gather all
accessible information on phytochemical, physicochemical,
and pharmacological investigations relevant to C. camphora.
All relevant articles are written in English up to 2022. The
search occurred between August 2020 and May 2021. The
keywords used were as follows: “C. camphora,”“chemical
component,”“Unani Medicine,”“Kafoor,”“preclinical stud-
ies,”“clinical trial,”“phytochemical,”“adverse effect,”“tox-
icity,”and “traditional.”Chemical structure images were
taken by PubChem. Standard Unani Medical Terminology
of WHO was reviewed to define the suitable Unani termi-
nologies. The scientific name and synonyms were authenti-
cated and reproduced using The Plant List (http://www
.theplantlist.org). A total of 464 papers and 21 books were
retrieved, 386 were excluded, and we included research and
review papers from the electronic database (Figure 1).
Twenty-one included Unani classical manuscripts, and
herbal pharmacopeial texts were consulted, including the
incorporation of Urdu translation of the traditional text-
books such as Makhzan al-Mufridat,Al Jami ul Mufradat
Al Advia Wal Aghzia (1197-1248 AD), Muhit-i-A’zam
(1806–1902 AD), Khazainul Adwiya, (19th century), and
Bustan ul-Mufridat,Kitab ul Mansuri (850-925 AD).
We collected data from traditional, classical Unani and
herbal pharmacopoeia literature and up-to-date reviews
and research to address a traditional and contemporary
overview of the application of C. camphora in various ail-
ments. We conducted this review to report most of the infor-
mation on C. camphora therapeutic and traditional uses for
several diseases. In addition, we also included a comparison
between therapeutic traditional uses and its current research
to prove its ethnomedicinal properties. Furthermore, the
mechanism of natural bioactive molecules isolated from C.
camphora was also highlighted. Preclinical and clinical trials
were also reviewed to prove the effect of C. camphora in var-
ious diseases. Because no previous publications have incor-
porated this type of information in the review article, this
review aims to overview and analyze the taxonomy, distribu-
tion, macroscopic description of the plant, various
2 Oxidative Medicine and Cellular Longevity
ethnomedicinal properties, therapeutic Unani applications,
natural bioactive molecules isolated from different parts of
the plant, present mechanism of action of natural bioactive
molecules, comparison of therapeutic Unani applications
proven currently by preclinical and clinical studies, gap,
and future recommendation.
Hence, the following are the primary contributions of
this study:
(i) Traditional Unani overview of C. camphora plants
such as temperament, ethnomedicinal properties,
therapeutic applications in various disease condi-
tions, adverse effects, corrective, substitute, and
Unani compound formulations containing C. cam-
phora with dose and therapeutic applications
(ii) Various natural bioactive molecules separated from
various parts of the C. camphora plant with their
structures and their mechanisms of action depiction
such as analgesic, anti-inflammatory, antioxidant,
and anti-allergic
(iii) We also highlighted current research carried out
in vitro, in vivo, and silico pharmacological studies
such as antioxidant, anti-inflammatory, anti-aller-
gic, antibacterial, antifungal activity, anxiolytic and
antidepressant, analgesic, anti-hyperlipidemic, anti-
fertility, hepatoprotective, antifertility, wound heal-
ing, prostaglandin synthesis inhibition, and
oestrogenic activities
(iv) We included preclinical and clinical studies of the
main active biomolecules to report the significant
use of C. camphora in day-to-day life. It also has a
prophylactic effect against the SAR-CoV virus as
per the study, and it is one of the main ingredients
of Arq Ajeeb compound formulation used as a pro-
phylactic inhaler to prevent COVID-19 infection
(v) This review also contributes toward comparative
therapeutic evaluation, research gaps, future recom-
mendations, and conclusions
2. Vernacular Name, Taxonomy, Distribution,
and Types of C. camphora
The vernacular name summarized in Table 1. Camphor tree
is a shrub or an evergreen tree [18] belonging to the family
Lauraceae, Laurales order, genus Cinnamomum, and species
camphora [14, 19]. Over 250-300 species of the genus are
Full-length articles and
pharmacopeia (n = 78)
Review article
(n = 22)
Pharmacopoeia
book
(n = 21)
Clinical
(n = 4)
preclinical
(n = 2)
Preclinical
(n = 21)
Clinical
(n = 4)
preclinical
(n = 4)
Phytochemical
(n = 8)
Single
(n = 21)
Compound
medicines
(n = 6)
Scientic
database
(n = 464)
book (n = 21)
Paper excluded
(n = 386)
Research article
(n = 35)
Figure 1: Flow diagram of type and inclusion and exclusion of the study.
3Oxidative Medicine and Cellular Longevity
distributed globally [20]. Twenty-six species are found in
India, and approximately 40 species are commonly used
for medical conditions. Leaves and stem bark are the sources
of medicinal activity. Cinnamomum zeylanicum,C. cam-
phora,C. burmannii,C. cassia,C. tamala, and C. verum spe-
cies are rice sources of aromatic oil [20, 21]. Camphor
(Kafoor) is an exudate of a camphor tree as per the descrip-
tion in Unani literature. Moisture or liquid comes out from
cracks or incision in the tree and freezes out as rust. It is also
expelled through the hole of the tree [12], or the wood of
that tree is chopped and soaked and heated in the water
causing sublimation [12]. It is clear crystal white with a
strong smell [8, 12]. Camphor is found naturally or artifi-
cially synthesized. The natural camphor is D-camphor,
whereas the synthetic one is L-camphor [22]. Authentic
Unani texts described numerous varieties of camphor. The
best type is Kaisuri followed by Riyahi. Kaisuri is found in
the city of Qaisr on the island of Tarindib, so the name has
been given Kafuri Kaisur [8]. There are three different kinds
of camphor: Formosa camphor [22], Borneo or Barus cam-
phor, and blumea or Ngai camphor. Borneo camphor is high
priced, and it is naturally formed in the stems of Dryobala-
nops camphor grown in Dutch Sumatra and sinks in water.
This is considered the best type. Borneo Camphor is high
priced, and it is naturally formed in the stems of Dryobala-
nops camphor grown in Dutch Sumatra and sinks in water,
and the third type is Blumea or Ngai camphor.
3. Macroscopic Description
Its opposite, frequently three-nerved, long petiolate, oblong
or ovate, 5- to 12.5-cm long, and 2.5 to 5-cm broad leaves
are usually three-nerved. Its flowers are tiny and hermaphro-
dite or produced via polygamy or abortion. Typically,
females are larger and have few components. Nine stamens
are there, unless they are aborted. The ovary is sessile, free
from the perianth, style is narrow, the stigma is discoid,
and the style is narrow or obscurely 3-lobed [18]. The fruit
is a berry with spreading, somewhat expanded perianth,
completely or partially deciduous segments, and less fre-
quently persistent seeds [18].
4. Description in Unani Literature
4.1. Temperament (Mizaj). Temperament is one of the
unique features and fundamental principles of the Unani
system of medicine [24]. All medicinal substance, plants,
animals, and minerals have their temperament. The temper-
ament of drugs is used as a tool to assess the actions and tox-
icological properties of Unani drugs. The medications were
divided into four groups based on their innate nature: hot
(Hārr), cold (Bārid), moist (Ratb), and dry (Yābis) in terms
of their effect on a moderate human body and four degrees
1, 2, 3, or 4 in terms of increasing intensity of action. As a
result, different scholars have claimed that its temperament
is variable [12]. The temperament of camphor is cold and
dry in the third degree [12, 14], cold second, and dry in
the third-degree [8].
4.2. Ethnomedicinal Properties (Afa’l). Camphor, adminis-
tered orally, has several pharmacological properties such as
expectorant (Munaffith-i-Balgham) [12]; stimulant (Muhar-
rik) [12]; brain and heart tonic (Muqawwi-i-Qalb wa Dim
a
gh) [12]; exhilarant of brain and heart (Mufarrih al- Qalb
wa Dim
agh) [15]; antipyretic (D
afi-i-Humm
a) [12, 16];
hemostatic (H
˙
abis-i-Dam); anti-pyretic for tubercular infec-
tion (H
˙umm
aDiqq) (a form of fever that gradually depletes
the body's fluids and weakens its organs, resulting in weight
loss) [12, 16]; antispasmodic (D
afi?-i-Tashannuj) [12];
astringent (Q
abid
˙) [12]; disinfectant (Mani'-i-'Ufunat) [15];
anaphrodisiac (Duf-i-Bah- [12]; constipation (Qabz) [12];
and carminative, reflux expectorant, which stimulate the
heart and respiratory system and analgesic and sedative to the
nervous system [13]. Additionally, the overview of ethnomedic-
inal properties, therapeutic applications in Unani medicine, and
pharmacological activities are mentioned in Figure 2 (https://
www.ayurtimes.com/cinnamomum-camphora/3/6/2022 and
https://plant.ces.ncsu.edu/plants/cinnamomum-caomphora/).
Table 1: Vernacular name of C. camphora.
Language Vernacular name Ref.
Unani medicine Kafoor [14, 16, 23]
Persian Kafur, Kafoor [14, 16, 23]
English Camphor, Bheemseni camphor (natural), Bomeo camphor [14, 16, 23]
Arabic Kafoor [14, 16, 23]
Germany Kampher [14, 16, 23]
French Camphre [14, 16, 23]
Hindi Duk, Ben, Guj, Kafoof [14, 16, 23]
Sanskrit Karpoor, Ghausar, Himavaluka [14, 16, 23]
Tamil Pachai Karpooram, Karpooran-Cheena, Karuppuram [14, 16, 23]
Gujarati Kapoor, Karpoor [14, 16, 23]
Telugu Pacha Karpooram, Cheen Karpooram [14, 16, 23]
Siddha medicine Karupporam [13]
Ayurveda medicine Karpura, Ghanasaara, Chandra, Chandra Praba, Indu, Tushaara, Gandhadravya [13]
4 Oxidative Medicine and Cellular Longevity
4.2.1. Topical Application. Topical application of camphor
has antiseptic [12] and massages externally and initially; it
has stimulant [12] rubefacient (Muhammir) and then anes-
thetic (Mukhaddir) [12] and analgesic (Musakkin-i-Alam)
ethnomedicinal properties [12, 16].
4.3. Therapeutic Application as per Unani System of
Medicine. As per Unani system of medicine, Camphor is
useful in respiratory, gastrointestinal, musculoskeletal, integ-
umentary, oral cavity, ear condition, eye diseases, and other
general conditions (Table 2).
5. Therapeutic Dose, Adverse Effects, and
Correctives of C. camphora in the
Traditional and Contemporary Era
Unani classical texts mention doses range from minimum to
182 [12] up to 250 mg to 550 mg. According to another
opinion 7 gm/week [15], the maximum dose is 364 mg to
728 mg. More than 8.75 gm reduces sexual power or may
cause death [16]. The minimum dose is 182 to 364 mg and
can be given for strengthening the patient [16]. The lethal
dose in adult humans is 5 to 20 g. One teaspoon of camphor-
ated oil (~1 mL of camphor) was lethal to 16 and 19-mont h-
old children [25]. Unani scholars stated that overdose or
misuse of this drug may adversely affect cold temperamental
people (Barid Mizaj) [12, 15, 16], stagnation of sperm (Mun-
jamid Mani), and weakness in individual’s stomach [15, 16]
that reduces sexual power and sperm quality and forms kid-
ney stone [12, 15, 16].
Camphor is quickly absorbed by the mucous mem-
branes, skin, and gastrointestinal tract in liquid form. Symp-
toms may appear 5–90 minutes after consumption. The rate
of absorption is heavily reliant on the existence of food and
other compounds [26]. In humans, intoxication signs are
abdominal distress, emesis, tremors, excitement, seizures,
and CNS depression characterized by apnea and coma [17,
25]. The traditional Unani medicine discusses various cor-
rective agents (Muslih) and forms of simple and compound
drugs that can use according to the condition internally or
externally to manage or minimize the adverse effects of cam-
phor. As camphor is cold temperament and to combat it
coldness, hot and aromatic herbs such as oil of Viola odorata
L. (Rogan-i-Banafsha), oil of Narcissus tazetta Linn (Rogan-
i-Nargis), Ambar, and Castoreum (Jundabedastar) [15, 16]
are used as corrective. Oil of Iris ensata Thunb (Roghan-i-
Sosan), [12, 16] a flower of Viola odorata L. (Gul-i-Banaf-
sha) [12], and a confection of Rosa damascene act as a cor-
rective in a condition such formation of renal stone caused
by camphor use [15]. Narcissus tazetta L. (Banafsha),
Nelumbo nucifera Gaertn (Niloufer), Crocus sativus, a con-
fection of Rosa damescene (Gulkand), Ambar, and Musk
are drugs that act as corrective in headache caused by use
of camphor [15].
6. Substitute (Badal)
The idea of drug substitution (Abdāl-i-Adwiya) is a signif-
icant criterion of Unani pharmacotherapy [27]. In Unani
Medicine, replacing the main drug with a substitute having
the same or closest pharmacological action with the first
desired drug and a substitute can be chosen depending
on the situation. Need for drug substitutes, Al-Razi sur-
mised that “frequently, all drugs needed for treatment are
not easily available everywhere. As a result, if a physician
is uninformed of the replacements that must be used in
Anti-inammatory
Analgesic
Anti microbial
Anti viral
Mucolytic
Anti oxidant
Immunomodulatory
Hepatoprotective
Estrogenic eect
Anxiolytic
Antidepressant
Inhibitory eect of prostaglandin
C.Camphora tree
Camphor crystals
Natural bioactive molecules
In-vitro/In-vivo/In-silico
Pharmacological properties
Steam distillation,
sublimation, purication
of wood, twig, bark, etc
erapeutic applications (Unani medicine)
Eye Cardio vascular Respiratory Mus culo -
skeletal
Ear
Gastrointestinal
Skin
Internal External application
Respiratory: Clear lung ulcers, Hectic fever
Coryza, Catarrh, Chronic cough, to stop
epistaxis
Pleurisy, Pneumonia
Gastrointestinal: Flatulence, diarrhoea,
Dysentery, Bilious diarrhoea Hepatitis
Musculoskeletal Joint pain and musculoskeletal pain
Ear Ear pain
Oral cavity Stomatitis, toothache, tooth decay
Eye: Irritation of eye, Su’ Mizaj Hārr of eyes,
Conjunctivitis (MA, 2018)
Integumentary Reduces irritation
General condition: Tubercular fever, evil heat
of soul, Acute fever from warm temperament
antidote to scorpion poison
Bilious headache
Waram-al-Hārrah and Sudda-i-Hārr
Wound and foot swelling
Camphor Cineole
Safrole
Citronellal Alpha-pinene
Eucalyptol
Limonene
Linalool
Figure 2: Overview of ethnomedicinal properties, therapeutic applications in Unani medicine, and pharmacological activities.
5Oxidative Medicine and Cellular Longevity
place of the principal drug, the medical profession’s objec-
tivity will be compromised”[28]. The great physician, Avi-
cenna states that a substitute can be used “When the
initially intended medicine is unavailable”[4, 29]. In case
of non-availability of Camphor, Barbarea vulgaris (Taba-
shir Sufaida) [12, 16, 30] or Pterocarpus santalinus (San-
dal) [15, 16] or fossil resin of Pinus succinifera (Kahruba)
[15] can use as a substitute.
7. Ethnomedicinal Properties and Therapeutic
Applications of Unani Compound
Formulations of Camphor (Murakkabat)
Compound medicines are pharmaceuticals that contain two
or more herbs as ingredients in a variety of dose formula-
tions and administration routes. Topical preparations
include ointment, lotions, and fine powders for ocular use.
Table 2: C. Camphora effect on system, therapeutic application, dosage form and method of use.
System Therapeutic application Dosage
form Method of usage Ref.
Respiratory
Pleurisy (Dhāt al-Janb) and pneumonia (Dhāt al-
Ri’a)
Epistaxis
Lung ulcers
Specific fevers (HummāDiqq)
Coryza, catarrh (Nazla-o-Zukām), and old cough
Oil External application with suitable oil
[8,
12,
15,
16]
Gastrointestinal
Flatulence (Riyāh-i-Mi῾da)
Passing loose stools due to the predominance of
yellow bile or blood (Ishāl-i-Safrāwi and Damwi)
It can also be used in dysentery, bilious diarrhea,
and inflammation of the liver (Waram al-Kabid)
——
[8,
12,
15,
16]
Musculoskeletal
Joint pain and accumulation of humor in the
distended muscle fibers causes soreness (Waja‘al-
Khāsira, and Waja‘al-Mafāsil)
Oil External application camphor powder mixed
with oil [12]
Integumentary Skin conditions and reduces irritation
Oil
Cream
(Marham)
External application with suitable oil or cream [12]
Oral cavity
Tooth pain Camphor
sublimation
Powder or powder with rose oil on affected
tooth
[12,
16]
Stomatitis and toothache (Qulā‘and Dānton ka
Dard)
Gargle and
mouth
wash
Camphor along with distillate water of Rosa
bourboniana (Arq-i-Gulab)[15]
Ear condition Ear pain Ear drop Camphor with fresh coriander juice (Aāb-i-
Kasneez Sabs)
[12,
15]
Eye diseases
Eye irritation
Abnormal hot temperament (Su’Mizaj Hārr) of
eyes.
Conjunctivitis and prevents eye involvement in
smallpox
Fine
powder
(Surma)
Fine
powder
(Surma)
Fine powder apply on eyelid
Fine powder with the juice of coriander
[12,
15]
General
condition
Fever due to tuberculosis
Exhilarant and cardiac tonic Powder -
[8,
12,
15,
16]
Bilious headache, evil heat of soul, and fever Paste
Location application of paste prepared by
mixing powdered camphor with rose oil and
grapes apply on the forehead
Antidote to scorpion poison Powder Powder with rose oil
It works in the hot type of inflammation (Waram-
al-Hārrah) and obstacles (Sudda-i-Hārr)
Oil or
ointment Camphor mixed with suitable oil
Epistaxis Nasal drops Camphor is used with Myrtus communis for
epistaxis
Wound and foot swelling
Dusting
powder,
ointment
—
6 Oxidative Medicine and Cellular Longevity
Oral preparations include pills, tablets, powder, and semi-
solid confection forms. Several Unani compound formula-
tions as per pharmacopoeia preparation possessing
different ethnomedicinal properties, therapeutic applica-
tions, and dosage forms with doses acting on different body
systems have been described in detail in Table 3.
8. Natural Bioactive Molecules of C. camphora
and their Mechanism of Action
Seventy-four compounds were discovered in leaf, branch,
wood, and root chromatograms of C. camphora tissues
[35]. Phytochemical components of C. camphora are pheno-
lics, flavonoids such as tannins (2.09%), saponins, alkaloids
(3.85%), and carbohydrates [36]. The bioactive compound
of C. camphora oil identifies the relevant analgesic effects
β-caryophyllene, α-caryophyllene, germacrene D, bicyclo-
germacrene, unidentified, nerolidol, spathulenol, and
unidentified (E)-α-atlantone [36]. Another study identified
96 various compounds in the essential oils by two-
dimensional gas chromatography such as methyl isobutyl
ketone, pinene (αand β), α-thujene, camphene, sabinene,
α-phellandrene, hexanal, 3-hexanal-1-ol, 1-hexaol, and sabi-
nene [37]. The major bioactive molecules of C. camphora are
camphor, linalool, safrole, and cineole. The major bioactive
molecules in different parts of the plant are mentioned in
Table 4 and Figure 3.
The pathophysiology of respiratory diseases (sinusitis,
asthma, bronchitis, and COPD) is mucociliary dysfunction,
inflammation-induced edema, and hypersecretion of goblet
cells that probably plays an important role. Cineole natural
substance from camphor has pharmacological properties
that are known to reduce inflammation, secretion of goblet
cells decreases, the ciliary beat frequency is sped up, and
bronchodilatory and mucolytic properties hence help in
the drainage of sinuses and other respiratory organs [3].
Consequently, cineole would be therapeutically beneficial
for asthma and bronchitis patients based on its proven
broncho-dilating and anti-inflammatory effects. Other stud-
ies also have proven the effect on cineole [41–44].
A new elucidation for the analgesic application of cam-
phor is the combination of transient receptor potential A1
(TRPA1) inhibition and desensitization of TRPV1. Cam-
phor activates and then desensitizes TRPV1, thereby having
an analgesic action. Linalool bioactive molecules showed
pain reduction in mouse models such as inflammatory pain,
acetic acid-induced writhing response, and the hot plate test.
The likely mechanism perhaps is related to its regulation of
NMDA receptors and suppression of pro-inflammatory
cytokines [36]. In a clinical investigation, topical borneol
treatment dramatically reduced pain compared to placebo.
Furthermore, an in vivo study in mice that exhibited TRPM8
channels may perhaps be the molecular target of borneol
[45]. C. camphora natural bioactive molecule menthol after
topical application (skin, mucous membrane, and oral and
nasal cavities) also activates TRPA1, s highly sensitive men-
thol receptor that contributes in counterirritants and analge-
sic activities. This suggests the involvement of different
kinetics of channels and fast desensitization due to these
sensory effects of menthol [46].
Clinical investigations and contemporary medical exper-
iments in migraine and vascular headache demonstrated the
crucial role of nitric oxide (NO). NO and nitric oxide syn-
thase (NOS) inhibitors can significantly reduce the severity,
frequency, intensity, and accompanying symptoms of
migraine attacks. A protein complex known as nuclear
factor-kappa β(NF-B) regulates DNA transcription, cytokine
synthesis, and cell viability. NF-κB induces the expression of
inducible nitric oxide synthase (iNOS), and overexpression
of iNOS can catalyze L-arginine to yield nitric oxide (NO).
Proinflammatory factors are also activated by NF-κB and
then cause a neurogenic inflammation reaction, which sensi-
tizes the pain center and initiates headache. In the pathogen-
esis of migraine, NF-κB has a significant mediating role. The
essential oil of camphor leaves in the mouse model showed
noteworthy analgesic action on migraine by inhibiting the
nuclear factor-kappa B (NF-κB)/inducible nitric oxide syn-
thase (iNOS) pathway and reduced neurogenic inflamma-
tion. Essential oil of C. camphor perhaps inhibits the iNOS
and expression of NF-κB and therefore decreases NO pro-
duction and neurogenic inflammatory response (Figure 4).
Therefore, it could treat migraine. The main analgesic com-
pounds recognized in the camphor’s essential oil camphor
leaves were nerolidol and (E)-α-atlantone [36]. Citronellol,
which affects cyclooxygenase (COX) 1 and 2, is the enzymes
involved in the production of prostaglandins from arachi-
donic acid and decreases the production of inflammatory
mediators which is related to its ability to reduce cell migra-
tion and paw edema [47].
Markel et al. [48] investigated the influence of camphor
on the expression of oestrogenic genes. They discussed
how the UV filter 4-methyl benzylidene camphor (4-MBC)
is oestrogenic and interferes with the thyroid axis. They dis-
covered that, in rats, exposure to 4-MBC altered the mRNA
levels of ER-alpha, progesterone receptor (PR), preproenke-
phalin (PPE), and insulin-like growth factor-I (IGF-I) in the
brain in a sex- and region-specific manner. Methanolic
extract of C. camphora contains anti-inflammatory mecha-
nisms that limit NO and PGE2 synthesis in LPS/IFN-acti-
vated macrophages and prevent the generation of TNF IL-
6 and IL-1 from RAW264.7 cell [10]. The proanthocyanidins
(PAs) in the leaves of C. camphora inhibit tyrosinase mono-
phenolase and hence have been proven to have anti-
tyrosinase activity. The PAs also showed strong antioxidant
capacity with the ferric reducing antioxidant power (FRAP),
scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 1,2′
-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS)
assays [49].
9. Preclinical and Clinical Studies of Main
Active Biomolecules
The preclinical studies of the main natural active biomole-
cules are summarized in Table 5. Table 6 summarizes the
preclinical and clinical studies of the compound formulation
of camphor.
7Oxidative Medicine and Cellular Longevity
Table 3: Unani formulations, dose, dosage form, ethnomedicinal properties, and therapeutic applications of C. camphora as one of the
ingredients in different body systems.
Unani
formulation Dose Dosage form Ethnomedicinal properties Therapeutic application Ref.
Respiratory system
Habb-i-
Nafs-ud-
Dam Silli
5-10 gm Pills
Hemostyptic (Habis-i-Dam),
healing agent (Mudammil),
Antipyretic (Dafi‘-i-Humma)
Nasal bleeding (Nafs-ud-Dam),
phthisis (Sill), asthma (Diq al-Rewi)[31]
Habb-i-
Jawahar
Muwallif
Khas
500 mg Pills
Tonic (Muqawwi), expectorant
(Munaffis-i-Balgham), analgesics
(Musakkin)
Phthisis, bronchial asthma [32]
Habb-i-
Khunaq 5-10 gm Pill Analgesics, anti-inflammatory
(Muhallil-i-warm)
Inflammation of bilateral pharyngeal muscle/
diphtheria (Khunaq), pharyngitis, and
laryngitis
[32]
Gastrointestinal system
Habb-i-
Qabid 125-250 mg Pills Astringent (Qabid), antiseptic
(Dafi‘-i-Ta‘affun)Infantile diarrhoea (Ishal al-Atfal) [33]
Qurs-i-
Atash 5-10 gm Tablet Anti-bilious (Dafi‘-i-Safra) Reduce thirst, acidosis (Humudat-i-Mi’da) [31]
Qurs-i-
Kafoor
Musik
5-10 gm Tablet Astringent Diarrhea [31]
Jawarish-i-
Kafoor 5-10 gm Semisolid
confection
Stomachic (Muqawwi-i-Mi’da),
carminative (Kāsir-i-Riyāh)
Dyspepsia (Su’al-Hadm) indigestion
(Tukhma), flatulence (Nafkh-i-Shikam)[31]
Habb-i-
Taoon
Qawi
250-500 gm Pill Antidote (Dafi‘-i-sumum)Plague (Ta‘un)
Food poisoning (Hayda)[32]
Habb-i-
Taiyub-ul-
fam
5-10 gm Pill Mutib-i-Dehan Halitosis (Bakhr al-Fam) [32]
Safuf-i-
kahruba 3-5gm Powder Digestive (Hazim), laxative
(Mulaiyin), appetizer (Mustahi)
Indigestion (Du’f‘-i-hadim), reduce thirst (Du‘f-
i-istiha) [23]
Habb-e-
Pechish
220 mg (one
pill) Pill Astringent and hemostyptic Dysentery, diarrhea [23]
Qurs-e-
Zaheer 2 tab twice Tablet Anti-dysenteric, stomachic Dysentery, indigestion (Dafi‘-i-Mi’da) [34]
Tiryaq-i-
Pechish
Jadid
3 gm twice a
day Powder Anti-diarrhea
Useful in bilious and phlegmatic dysentery
(Zahīr Safrawi), Wa Balghami), Chronic
dysentery (Zahīr Muzmin)
[34]
Marham-i-
Bawaseer
Q.S. for
external use Ointment Prevent piles (Dafi‘-Bawasīr)
Burning sensation of hemorrhoid (Sozish-i-
Bawasīr), painful hemorrhoid (Waj-ul-
Bawasīr), bleeding piles (Bawasīr Damya)
[34]
Marham
Saeeda
Chob
Neemwal
Q.S for external
us Ointment Anti-inflammatory Hemorrhoid [31]
Eye
Jauhar-i-
Naushadar Q.S Semisolid
sublimation Detergent (Jālī), analgesics Keratitis (Sabal), corneal opacity (Bayād),
pterygium (Zufra) (for ophthalmic use) [31]
Kohal-i-
Kafoor Q.S
Finest
powder (for
ophthalmic
use)
Resolvent (Muhallil-i-Waram) Conjunctivitis, burning sensation of eye [31]
Burood-i-
Muqawwi-
i-Basar
Q.S Fine powder
(for Eye tonic (Muqawwi-i-Basar) Asthenopia/amblyopia (Dafi‘-al-Basar) [31]
8 Oxidative Medicine and Cellular Longevity
Table 3: Continued.
Unani
formulation Dose Dosage form Ethnomedicinal properties Therapeutic application Ref.
ophthalmic
use)
Burood-i-
Sozish-i-
Chashm
Q.S
Fine powder
(for
ophthalmic
use)
Refrigerant (Mubarrid), analgesics Burning sensation of the eye (Sozish-i-
Chashm), eye irritation (Kharish-i-Chashm)[31]
Kohlul
Jawahar Q.S Past Eye tonic Weakness eyesight (Duf‘-i-Basar) [31]
Cardiovascular system
Mufarrah
Shaikh ur
Rais
5gm Semisolid
confection Cardiac tonic (Muqawwi-i-Qalb)Weakness of heart (Du’f al Qalb) and
palpitation (Khafqan)[31]
Integumentary system
Marham
Kharish
Jadeed
Q.S for external
us Ointment Refrigerant and antibacterial (Qatil-
i-Jara’sim)
Fungal infection (Dād), ringworm (Qūbā),
irritation (Kharish), itching (Hikkah), and
blood infection (Fasad-i-dam)
[31]
Marham
Kafoor
Q.S for external
us Ointment Refrigerant, antiseptic Ulcer (Qurūh) and inflammatory wound [31]
Marham-e-
Safaida
Kafoori
Ointment
Healing agent (Mudammil),
antiseptic (Dafi‘-i-Ta‘affun), wound
(Qurooh-i-Afni)
Wound [31]
Reproductive system
Jauhar-i-
Kafoor
125 mg in a
capsule
Dried
powder Antiseptic, refrigerant (Mubarrid) Gonorrhoea (Sozāk) [31]
Halwa-i-
Suparipak 10-20 gm Semisolid
preparation
Spermatogenic (Muwalliz-i-Mani),
retentive of semen (Mumsik),
aphrodisiac (Muqawwi-i-Bah)
Spermatorrhoea (Jarayan), nocturnal emersion
(Surat-i-Inzal), loss of libido (Du’f al Bah)[31]
Nervous system
Jauhar-i-
kafoor kawi For inhalation Semisolid
sublimation Nervine tonic (Muqawwi dimagh) Convulsion (Sara), syncope (Ghazhi) [32]
Miscellaneous
Qurs-i-
Sartan-
Kafoori
3-5 gm Tablet Hemostyptic, antipyretic
Type of bilious fever with excessive thirst and
bilious vomiting (Hummā-i-Muharraqa),
tuberculosis (Dīq), cough, phthisis
[31]
Qurs i-
kafoor Lulvi 2-4 gm Tablet Antipyretic, healing agent,
expectorant, astringent
Acute fever (Hummāal-hadda), phthisis, hectic
fever (Hummādiq), gastrogenic diarrhea (Ishal
mi‘di)
[32]
Habb-i-
kafoor
marwareed
500 mg Pills Antidote, antipyretic Fever, epidemic fever (Hummā- Waba’iyya) [32]
Hab-i-Tap-
i-larza 150-250 mg Pill Antipyretic Type of fever (Hummā-i-Ejamia) [32]
Hab-i-
kafoor 125-250 mg Pill Antipyretic Hummā-i-muharraqa [23]
Qur-i-
kafoor
Four tablets
(each 775 mg) Tablet Refrigerant Hectic fever and bilious fever [31]
Habb-i-
Ikseer
Bukhar
400 mg thrice a
day with
lukewarm
water
Pill
Antipyretic for fever with chills
(Dafi‘-tap-i-Larza)
Antipyretic for seasonal fever (Dafi‘-
i-tap-i-Mausami)
Continuous fever
Seasonal fever [34]
Q.S.: quantity as required.
9Oxidative Medicine and Cellular Longevity
Table 4: Natural bioactive molecules found in different parts of the C. camphora tree.
Part of the tree Major natural bioactive molecules
Camphor 1,8-
Cineole Linalool Citronellal α-
pinene Camphene Safrole β-
pinene Limonene Eucalyptol α-Terpineol or
terpineol
D-
borneol References
Leaf oil + + + + + + [18]
Branch + + + [18]
Wood essential oil + + + + [18]
Root essential oil + + + [18]
Essential oil from leaf and branch
mixture + + + + + + + [18, 38]
Essential oil from wood, leaf and
branch mixture + + + + [18]
Twig essential oil + + [37]
Seeds oil + + + [37]
Fruit oil + + + [37, 39]
Fresh leaves + [10, 40]
10 Oxidative Medicine and Cellular Longevity
9.1. In Vitro Pharmacological Properties. Numerous in vitro
experimental studies show that antioxidant, antimicrobial,
anti-inflammatory, and miscellaneous activities have been
demonstrated by numerous research on C. camphora.
9.1.1. Antioxidant Activity. By interacting with biological
components within the cell, the oxidation process damages
cells, resulting in a variety of illnesses and chronic diseases
like cancer and cardiovascular conditions. Additionally, oxi-
dation changes the nutritional value and safety of food by
producing secondary reaction products [58]. Oxidative
stress is a condition when antioxidant levels are low. Antiox-
idant activity of polyphenols, which is influenced by their
polyphenolic structure, has the effect of removing free radi-
cals and improving antioxidant activity [59]. Due to an
excess of reactive oxygen species (ROS), oxidative stress
develops when the body’s antioxidant system becomes
depleted. Due to this, an increase in the concentration of free
Camphor Cineole Linalool Safrole
Citronellal
Alpha-pinene
Eucalyptol NerolidolBorneol
𝛽-thujone 𝛽-pinene
Limonene
Figure 3: Bioactive molecules in C. camphora.
Inammatory response/
inammation inhibits
Chemokine &
inammatory
cytokine
production
Nucleus
DNA
translation
NF-𝜅B
activation
TNF Alpha
IL-6, IL-1
COX-2
iNOS NO synthesis
PGE-2
production
e major analgesic
compound are nerolidol
and (E)-𝛼-atlantone
Guarytyl
synthesis
GTP
GMP
Biological
eect
TRPV1
Analgesic activity
Menthol
TRMP8
channel
NF-𝜅BP
Psychophysical
sensations on
topical app lication
of menthol to the
skin-sensory
eect
Cineole
Citronellal
Decreases
Borneol
Inhibits
Analgesic activity
Activat es
TRPA1
In-vivo
Inhibition
Desensitization
CAMPHOR
Borneol
Migraine &
headache
Neurogenic
inammation
Inhibits
Camphor
Figure 4: Anti-inflammatory and analgesic mechanisms of action of natural bioactive molecules of C. camphora.
11Oxidative Medicine and Cellular Longevity
radicals inside cells is the root cause of many chronic disor-
ders such as nonalcoholic fatty liver, type 2 diabetics, neuro-
logical conditions, and reproductive-related problems
[59–61]. Reactive oxygen species (ROS) at baseline levels
are necessary for basic physiological activities. Ageing, obe-
sity, type 2 diabetes mellitus (T2DM), depression, and neu-
rodegeneration are all conditions that are significantly
impacted by oxidative stress [59] (Figure 5). Camphor has
antioxidant, hepatoprotective, antidepressant, estrogenic,
and anti-inflammatory qualities in addition to being an anti-
oxidant that prevents oxidative damage and neutralizes free
radicals. Camphor’s antioxidant capabilities may lessen tis-
sue damage and oxidative stress. In scavenging DPPH,
ABTS, and ferric reducing antioxidant power (FRAP) assays,
the phytochemical proanthocyanidins (PAs) from leaves and
branches of C. camphora displayed significant antioxidant
activity [49]. The antioxidant activity of hexane, chloroform,
and ethanol extracts was determined using the DPPH (2,2-
diphenyl-1-picrylhydrazyl) technique on dried camphor
leaves. Another study evaluated the antioxidant activity of
leaves of C. camphora in three different solvents and was
tested by using the DPPH method, and hot extraction
(Soxhlet) and cold extraction (maceration) methods were
applied for the presence of components in the camphor
leaves. The antioxidant activity of ethanol extracts was
higher than that of other extracts. These findings show that
camphor leaves, which have significant antioxidant quality,
are excellent for pharmaceutical composition. Linalool, ner-
olidol, and borneol are the phenolic compounds extracted
from the ethanolic extract. The hot extraction method by
using ethanol solvent can extract antioxidant and mineral
content against camphor leaves [62] (see Figure 6). Liu et al.
[63] established the flavonoids extracted from C. camphora
leaves’in vitro antioxidative capacity. Both the ferric reduc-
ing antioxidant power assay and the 1,1-diphenyl-2-picryl-
hydrazyl (DPPH) free radical scavenging assay
demonstrated a dose-dependent increase in antioxidant
activity in the flavonoids, which is outstanding compared
to commercial antioxidants [64].
9.1.2. Antimicrobial. Numerous disorders in the body are
brought on by pathogens, which are inhibited by antimicro-
bial agents, which also stop the establishment of microbial
colonies. One of the biggest problems in human health is
the over and improper use of antibiotics. Additionally, the
rapid spread of microorganisms that are resistant to antibi-
otics is concerning. The herbal potential of C. camphora is
recognized to serve as an antibiotic, antiviral, and antifungal.
Wang et al. [65] described that there is evidence that C. cam-
phora essential oil has therapeutic properties like antibacte-
rial effects. The obtained MICs and MBCs verified the
clinical strains’significant susceptibility to CCEO. The
development of E. coli biofilms is intimately associated to
prolonged E. coli infection and can lead to antibiotic resis-
tance. E. coli was significantly destroyed by CCEO, and the
E. coli biofilm was also effectively destroyed. C. camphora
essential oil (CCEO) was active against E. coli in suspension
and biofilms, two states that are common in living organ-
isms. Escherichia coli, one of the most frequent microbial
pathogens, is mainly responsible for biofilm-associated
Table 5: Preclinical (in vitro/in vivo/in silico) and clinical studies of C. camphora and its main natural bioactive molecules.
Natural
bioactive
molecule
Methodology Test drug Control Result Pharmacological activity
/disease Ref.
Camphor Cell line study (male
Wister rat DRG cells)
Dorsal root ganglion
of adult male Wistar
rats
Crt wash
Activate TRP receptor
(TRPM8) and mutant
channel
Analgesic by
cold and heat
sensitization of camphor
[50]
Citronellal
Rat module in vivo
and in vitro (paw
edema and peritoneal
fluid leucocyte count)
50,100,200 mg/kg Dexamethasone
(2 mg/kg, s.c.),
In vitro and vivo studies of
citronellal significantly
(p<0:01) reduce paw
edema and leucocyte count
Anti-inflammatory and
analgesics [47]
Clinical trials
Cinelol Randomized, double-
blind, clinical trial
100 mg capsule three
daily for 7 days Placebo
Symptom (headache,
heaviness, secretion, and
nasal obstruction) reduced
Acute non-purulent
rhinosinusitis [42]
Cineole
Randomized placebo-
controlled trial
(multicenter)
200 mg cineole or
placebo 3 times for
six months during
(concomitant
therapy)
Placebo
Significant improvement
notes test group
Improvement in dyspnea,
lung function
Anti-asthmatic [43]
Cineole
(Eucalyptol)
Randomized placebo
controlled clinical
trial
200 mg cineole or
placebo 3 times for
six months during
winter
Placebo
Improve lung function and
health status. Reduce
exacerbation and dyspnea
COPD [44]
Cinelol
Randomized placebo-
controlled clinical
trial
3 × 200 mg of
cineole, per day for
10 days
Placebo control Significantly reduce cough
p=0:0001 Bronchitis [41]
12 Oxidative Medicine and Cellular Longevity
Table 6: Unani compound formulations with C. camphora and pharmacological application in preclinical (in vitro/in vivo/in silico) and
clinical studies.
Unani formulation Method/
model
Extract use/dosage
form
Control/
organism
tested
Result Pharmacological
application Ref.
Preclinical studies
Arq-Ajeeb In vivo (rats) 0.07 ml and
0.14 ml/kg, p.o.
Charcoal
administration Reduce diarrhea in rats Anti-diarrheal
activity [51]
Compound
preparation of
sesame oil,
camphor, and
honey
Animal (rat) Daily dressing with
extract Oil Vaseline Maximal healing was noticed in
the test group
Healing effect of
second-degree burn [52]
Arq Ajīb contains
methanol, camphor
In silico
approach
Inhibits SARS-
CoV-2 spike
glycoprotein and
main protease
—
Good interactions and binding
affinities with 3CLpro and S
glycoprotein
Inhibitory effect on
SARS-CoV-2 [53]
Extract C.
camphora and
Ziziphora tenuior
In vitro mice
liver
3, 5, 10, 25, 50, and
100 mg/ml of
extracts
—
The extract exhibited dose-
dependent and time-dependent
antiparasitic effects
Anti-parasitic and
immunomodulatory [54]
Clinical studies
Marham-i-Raal
Single-arm
pre- and
posttreatment
study
2 gm on episiotomy
wound
—REEDA score decreased, and
VAS score decreased
Episiotomy wound
healing and pain
reduction
[55]
Marham-i-Raal Case study
External
application (3
months)
(ointment)
—Completely heal foot ulcer Chronic wound
healing [21]
Arq Ajib Clinical study Liquid application —Decrease in VAS score for pain
intensity Headache [56]
Composition of A.
indica and C.
camphora
Controlled
clinical trial Oral and topical
Psoralen plus
ultraviolet A
(PUVA)
solution
In individuals with moderate-to-
severe CPP, test medications that
are efficacious and well-tolerated
Chronic plaque
psoriasis [57]
Norma l cell
Oxygen depleted cell
Oxidative stress
Cell damage
leads cancer
Type 2 diabetics
and complications
Liver damage
Cardiovascular
disease
Neurological
and
reproductive
conditions
Non-enzymatic
antioxidants
LMWA, Plant
oxidants
Antioxidant
defense
Enzymatic antioxidants
SOD, calatase, Gpx,
Grx, G6PD, xanthine
oxidase
Presents free radical
Dietary sources
-Vitamins A, E, C,
-Carotenes
Natural bioactive
molecules
-Bioavonoids
-Polyphenols
Camphor contains
phenolic are
Linalool, nerolidol and
borneol
Figure 5: Oxidative stress affects various systems and antioxidant defenses including natural bioactive molecules.
13Oxidative Medicine and Cellular Longevity
opportunistic illnesses like diarrhea, endometritis, and mas-
titis [65]. In another in vitro study of camphor ethanolic
extract has been showed antibacterial action against Escher-
ichia coli,Staphylococcus aureus, and Pseudomonas aerugi-
nosa [56]. Poudel et al. [37] analyzed in vitro study of C.
camphora essential oil against five Gram-positive bacteria,
Streptococcuspyogenes,Propionibacteriumacnes,Bacilluscer-
eus,Staphylococcusepidermidis, and Staphylococcusaureus,
and two Gram-negative bacteria, Pseudomonas aeruginosa
and Serratia marcescens, showing its antibacterial proper-
ties [37].
The phytochemical compounds found in C. Camphora
have a wide variety of antibacterial properties against various
pathogens. Leaf, branch, and wood essential oil were tested
again using seven strains of fungi, Aspergillus niger,Aspergil-
lus fumigatus,Candida albicans,Microsporum canis,Tricho-
phyton mentagrophytes,Microsporum gypseum, and
Trichophyton rubrum.Serratia marcescens responded favor-
ably to the wood essential oil’s antimicrobial properties.
Camphor, 1,8-cineole, -terpineol, and safrole were the main
ingredients in the wood oil; hence, the reported activity of
the wood oil against S. marcescens may be the result of syn-
ergism between these and other constituents. Only a small
amount of action was seen against S. marcescens by cam-
phor, 1,8-cineole, -terpineol, and safrole. According to one
study, camphor and 1,8-cineole work together to have a syn-
ergistic antibacterial effect [35]. All fungi were cultured on
yeast malt, and studies showed good antifungal activity
against Aspergillus niger and Aspergillus fumigatus, while
the leaf essential oil showed good antifungal activity com-
paratively to other parts of the plant [35]. Kulzam is a
well-known Unani liquid composition used to cure several
ailments such as cough, colds, and sore throats [66]. The
major components identified in Kulzam were camphor,
menthol, etc. The ingredients of the formulation are Sat-i-
Pudina,Sat-i-Ajwain,camphor,Roghan baid majnun,
Roghan-i-darchini,Roghan-i-zaitun, and Roghan-i-laung.
Kulzam demonstrated a significant effect on all tested micro-
organisms at both 100 and 150 (micro) levels of the undi-
luted formulation (test sample), and at 150 (micro) level, it
inhibited growth more than the standard. Furthermore, it
highlights the fact that gram-negative microorganisms are
more vulnerable to inhibitory activity than gram-positive
ones. Comparing the formulation to that of standard clotri-
mazole, it showed a very significant zone of inhibition
against the fungus Candida albicans and Aspergillus fumiga-
tus [66]. In an in vitro investigation, essential oil from C.
camphora leaves, flowers, and twigs showed antifungal
action again 7 strains including Aspergillus clavatus,Asper-
gillus niger,Chaetomium globosum,Cladosporium cladospor-
ioides,Myrothecium verrucaria,Penicillium citrinum, and
Trichoderma viride in 1000 μg/ml concentration [67]. In
addition, when compared to other sections of the plant, the
leaf oil exhibited the best antifungal efficacy [67]. Five locally
gathered plant species’fresh leaves were hydro distilled
using Clevenger’s apparatus to separate the essential oils
and stored in a glass jar. Using the poisoned food approach
on a potato dextrose agar medium, the oils were evaluated
for resistance to Aspergillus flavus at 5000 ppm. Only the
oil of C. camphora showed absolute fungitoxicity against
the test fungus among the five essential oils examined [55].
Studies showed camphor oil possesses mycostatic applica-
tion against Aspergillus flavus [68]. According to Karashima
et al. [46], CHO cell showed induce expression of TRPA1,
0.5 mg/ml tetracycline was added to the culture medium,
and cells were used 5–24 h after induction and menthol used
as test drug. C. camphora constituent menthol activates
TRPA1 and inhibits it in mouse neuron in in vitro study,
FRAP
ABTS
DPPH
Hexane,
chloroform &
ethanol plant
extract (DPPH,
hot (soxhlet) and
cold extraction
method)
C. camphora leaves
Plant extract as
natural Anti oxidant
Linalool
PAs (leaves &
branches)
Antioxidant
property of
C. comphora
Natural bioactive molecules
Borneol
Nerolidol
Solvents
Antioxidant
methods
(ABTS,
FRAP, DPPH)
Figure 6: Antioxidant activity of natural bioactive molecules of C. camphora.
14 Oxidative Medicine and Cellular Longevity
suggesting the involvement of different kinetics of channel
and fast desensitization due to these sensory effects of men-
thol, a widely used additive in counterirritants and analgesic
activity.
9.1.3. Anti-Inflammatory and Prostaglandin Synthesis
Inhibition. Inflammation is a healing process that is trig-
gered by pathogen, toxins, and radiations. These factors set
offthe immune system and cause inflammatory reactions
in the organs of the host, which may result in cell death
and/or illness. Unani traditional medicine is potentially use-
ful for the treatment of inflammation-related diseases, such
as rheumatism, bronchitis, asthma, COPD, acute non-
purulent rhinosinusitis, dermatitis, neurodegenerative dis-
eases, and muscle pains. There are well-known anti-
inflammatory compounds that have been extracted from
plants and evaluated in human clinical trials. Cinelol, cine-
ole, citronellal, and camphor make up the majority of them
[41–44]. Numerous investigations have revealed that C.
camphora has an anti-inflammatory activity in vitro. An
in vitro investigation of C. camphora leaf extract indicated
that it reduced the generation of inflammatory chemokines.
Its leaves had a significant impact on 2,4-dinitrochloroben-
zene-induced atrophic dermatitis in mice. An in vitro inves-
tigation of C. camphora leaf ethanolic extract indicated that
it reduced the generation of inflammatory chemokines. Its
leaves had a significant impact on 2,4-dinitrochloroben-
zene-induced atrophic dermatitis in mice. Lee et al. exam-
ined the inhibitory impact of CCex on IFN- (10 ng/mL)
stimulated HaCaT keratinocytes’ability to produce the
inflammatory chemokine (MDC). The outcomes demon-
strated that CCex inhibited MDC formation by IFN- in a
concentration-dependent manner. The MeOH extract of C.
Camphora inhibited prostaglandin E2 (PGE2) production
in LPS/IFN-activated macrophages by up to 70%. To further
understand C. camphora’santi-inflammatory activity,
researchers looked at macrophage-mediated inflammatory
events like cytokine production, NO release, PGE2 release,
functional activation of adhesion molecules, and oxidative
stress. It can have a strong immunomodulatory influence
on numerous inflammatory responses at the transcriptional
level, according to the findings of the study [10]. Methanolic
extract of C. camphora contains anti-inflammatory mecha-
nisms that limit NO and PGE2 synthesis in LPS/IFN-acti-
vated macrophages and prevent the generation of IL-1, IL-
6, and TNF- from RAW264.7 cells [10].
By interacting with biological components within the
cell, the oxidation process damages cells, resulting in a vari-
ety of illnesses and chronic diseases like cancer and cardio-
vascular conditions. Additionally, oxidation changes the
nutritional value and safety of food by producing secondary
reaction products [64]. The effectiveness of EOC derived
from leaves in treating allergic inflammation, such as atopic
dermatitis, was described by Kang [69]. The extract signifi-
cantly reduced inflammation in low-calcium, high-
temperature human adult keratinocytes and improved 2,4-
dinitrochlorobenzene-induced atopic dermatitis in mice.
These results will make it easier to create EOC as a novel,
all-natural treatment for inflammatory skin disorders [69].
9.1.4. Anti-Hyperlipidemic Activity. Camphor compound
was examined in rats with experimental dyslipoproteinemia
for its pharmacotherapeutic efficacy, antioxidant, and anti-
coagulant action. The positive results of the study allowed
this substance to be recommended for the prevention of ath-
erosclerotic damage to the vascular endothelium and the
prevention of thrombogenesis [70].
9.1.5. Antifertility Activity. In order to understand the
impact of camphor as a male local contraceptive, in-vitro
effect of camphor on human sperm vialbility and motility
was examined. A decrease in sperm motility and viability
in an in vitro investigation where camphor was used indi-
cates that fertilization efficacy is reduced. Camphor may
work as a contraceptive effect. The sperm motility and via-
bility decrease are probably because of a fall in fructose levels
or denaturation of protein and cholesterol, which are the
energy sources for sperm motility [71].
9.2. In Vivo Pharmacological Studies
9.2.1. Wound Healing Activity. Camphor, a potent wound
healing and ant wrinkle drug, reduced MMP1 expression
but increased collagen and elastin expression in UV-
exposed mouse skin after 4 weeks of therapy. Camphor
might prevent the loss of elastin and help it recover after
UV-induced damage to retain skin suppleness [60]. It also
decreased the depths of the epidermis and subcutaneous
fat layer in UV-exposed mouse skin. The ethyl acetate solu-
ble fraction of an ethanolic extract of C. camphora leaves in
Wister rats showed improvement in wound healing and
increased wound contraction due to enhance and acceler-
ated activity of fibroblast and epithelial cell migration to
the wound site and early dermal and epidermal regenera-
tion. Furthermore, the treated group also showed a consider-
able increase in collagen content [75].
9.2.2. Anti-Testosterone Activity. Jugular vein samples were
taken for hormonal analysis from Awassi lambs and rams
fed C. camphora at a dose of 20 mg/kg/animal, and semen
samples were collected from the animals using artificial
vagina in the control group. The study found that the testos-
terone hormone concentration in the treatment group was
much lower than in the control group, which could be attrib-
uted to camphor’s oestrogenic impact, which reduces testos-
terone hormone levels. Camphor may suppress
catecholamine secretion by inhibiting nicotine acetylcholine
receptors, which has an influence on male sexual behavior
and reproductively via its effect on blood testosterone levels
and/or the sympathetic nervous system. During the second
and fourth weeks of the experimental study, mass activity
in the camphor group was significantly (P<0:05) lower than
in the control group, whereas the individual sperm motility
percentage showed no significant differences between the
camphor and control groups throughout the entire experi-
mental period, i.e., over the final three weeks of the trial,
the camphor group displayed lower levels testosterone [73].
9.2.3. Oestrogenic Effect. Maerkel et al. [48] evaluated the
estrogenic effect on the brain and reproductive organs both
15Oxidative Medicine and Cellular Longevity
prenatal and postnatal exposure to UV filter 4-
methylbenzylidene camphor (4-MBC) in rats. Following
pre- and postnatal exposure to the UV filter 4-MBC, the cur-
rent study found alterations in the expression level and
estrogen sensitivity of target genes as well as in the steroid
receptor coactivator SRC-1 in sexually dimorphic brain
areas of adult rat offspring. They discussed how the UV filter
4-methyl benzylidene camphor (4-MBC) is oestrogenic and
interferes with the thyroid axis. They found that 4-MBC
exposure changed the mRNA levels of ER-alpha, progester-
one receptor (PR), preproenkephalin (PPE), and insulin-
like growth factor-I (IGF-I) at the brain level in rats in a
sex- and region-specific manner [48].
9.2.4. Anti-Allergic Activity. Edema, a dysfunctional skin
barrier, and the invasion of several inflammatory cell types
are the hallmarks of allergic skin inflammation, such as
atopic dermatitis (AD). In vivo,C. camphora leaves
(100 mg/kg) improved atopic dermatitis symptoms by low-
ering serum immunoglobulin E levels, reducing lymph node
thickness and length, decreasing ear edema, and lowering
the number of inflammatory cells infiltrating the ears. Atro-
phic dermatitis is an allergic inflammatory disorder that can
be treated with the leaves of C. camphora. IFN-γ, an impor-
tant mediator of immunity and inflammation, induces the
Janus tyrosine kinases- signal transducer and activator of
transcription (JAK-STAT) signal pathway. The investigators
reported that in skin inflammation lesions, leaf extract
inhibited macrophage-derived chemokine (MDC/CCL22)
production via the downregulation of (STAT) 1 and extra-
cellular signal-regulated kinase 1/2 (ERK1/2) pathways
and, hence, improved several symptoms (ear edema and
lymph node size) change in blood parameter (serum IgE)
and histological changes in mice with allergic dermatitis.
By administering DNCB to mice, we established experimen-
tal AD in order to research the effects of CCex on AD
in vivo. IgE levels are correlated with the severity of AD
and are linked to defective skin barrier, making IgE a key
therapeutic target for AD. When compared to the induction
group in this investigation, the CCex-treated group had con-
siderably lower serum IgE levels (p0:001). Comparing the
cutaneous edema in the CCex-treated mice to that in the
induction mice on day 29, the difference was significant
(p0:001). Additionally, the CCex-treated group showed con-
siderably less epidermal thickness and inflammatory cell
infiltration than the induction group [69].
9.2.5. Anxiolytic and Antidepressant Activity. Antidepressant
and anxiolytic medications are used to treat depression and
anxiety. Albino mice weighing 18-30 gm were used for the
study CCO given three different doses 250 mg/kg CCO
orally, 500 mg/kg, and 750 mg/kg CCO orally in each group.
and imipramine15mg/kg given intra peritoneal as a standard
control. C. camphora oil (CCO) showed significant anti-
anxiety and antidepressant effects compared to the control
group in rat models. Numerous monoterpenoid compounds
in the essential oil of C. camphora are confirmed by phyto-
chemical studies. β-thujone, β-pinene, linalool, and limo-
nene are monoterpenoids that are testified to have
antidepressant applications. Furthermore, recent research
has proposed the antidepressant action of β-pinene, which
increases dopamine level and inhibits MAO activity in rab-
bits. Additionally, few studies showed that numerous biolog-
ically active molecules, including monoterpenoids, are
potent inhibitors of MAO-A and MAO-B [9] (Figure 8).
9.2.6. Antioxidant Activity. As previously mentioned, C.
camphora seed kernel oil increased the concentrations of
superoxide dismutase and catalase in diet-induced rats,
which consequently boosted antioxidant activity and
reduced malondialdehyde concentration (a biomarker of
lipid peroxidation and oxidative stress) [64].
9.2.7. Analgesic Activity. C. camphora leaf essential oils
showed a significant analgesic effect against nitroglycerin-
induced experimental migraine in mice models and inhib-
ited the nuclear factor-kappa Beta, inducible nitric oxide
synthase, and nitric oxide pathway [36].
9.2.8. Hepatoprotective Activity. According to Johari et al.
[74], camphor powder solution given female rats by intra-
peritoneal injection for 14 days showed hepatoprotective
activity in the treatment of a deferent type of liver condi-
tions. On the liver enzymes, it is proven to have a stimulat-
ing impact. However, the researchers recommended that
camphor use in a higher dosage uninterruptedly probably
leads to a substantial increase in the concentration of liver
enzymes [74].
10. Toxicity Studies
C. camphora essential oil from seeds, twigs, and leaves
showed robust contact toxicity against cotton aphids with
median lethal concentration (LC50) values of 146.78,
274.99, and 245.79, mg/L after 48 h of treatment, respectively
[37]. Camphor is quickly absorbed by the mucous mem-
branes, skin, and gastrointestinal tract in liquid form. Symp-
toms may appear 5–90 minutes after consumption [26]. In
humans, indications of intoxication include nausea, vomit-
ing, trembling, and convulsions, which are followed by
CNS depression characterized by apnea and coma [17, 75].
11. Discussion and Comparative
Therapeutic Evaluation
Unlike petroleum products, camphor is a botanical hydro-
carbon, very inexpensive, and can be easily cultivated with-
out any shortages. Therefore, camphor is an exceptional
carbon source for the production of high purity, high yield,
and high efficiency [76]. According to Unani physicians,
seven factors are responsible for the maintenance of health,
and loss of any one of these can lead to disease or even death.
Dietotherapy and pharmacotherapy are mainly used to
maintain the equilibrium of humors to maintain health
and treat disease conditions. All single drugs have specific
and many ethnopharmacological properties according to
their active principles and temperament. C. camphora (L.)
is a traditional Unani medicinal plant with a third-degree
cold and dry temperament and hence useful in hot
16 Oxidative Medicine and Cellular Longevity
temperamental individuals [8] used since ancient times.
Nowadays, natural and artificial camphor is also used for
medicinal conditions and commercial purposes. A review
of Unani and other conventional literature realized that C.
camphora has prophylactic and several pharmacological
properties for treating medical conditions and strengthening
mental and physical properties and it is effective in treating
respiratory conditions, musculoskeletal, gastrointestinal,
oral, eye, integumentary, and general conditions. Unani phy-
sicians evaluated ethno-pharmacological properties, usage,
patient temperament, and disease condition when prescrib-
ing medications and then selected single pharmaceuticals
with correctives (Muslih) to reduce undesirable or unwanted
effects. Furthermore, to combat the adverse effect of cam-
phor on cold temperamental people [12, 15, 16], they
advised camphor with hot temperament and fragrance herbs
such as Zafran,Amber, and Misk [15].
Camphor’s distinctive aroma has led to its widespread
use in ointments and inhalants, particularly as a remedy to
treat respiratory ailments. Unani physicians stated that C.
camphora is commonly used in respiratory conditions such
as acute and chronic cough, fever, common cold, lung ulcers,
pleurisy, pneumonia, coryza, and catarrh in various forms as
a single drug or with another herbal, mineral, or animal ori-
gin drug as a compound formula as it possesses expectorant,
antipyretics, deobstruent, and mucolytic properties [8, 12,
15, 16]. C. camphora has been a useful remedy in symptoms
of COVID-19 and inhibits SARS CoV-2 spike