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Journal of Ethnopharmacology 142 (2012) 319330

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Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jep

Review

The genus Commiphora: A review of its traditional uses, phytochemistry


and pharmacology
Tao Shen a, Guo-Hui Li b, Xiao-Ning Wang a, Hong-Xiang Lou a,n
a
b

School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China
Department of Pharmacy, Jinan Maternity and Child Care Hospital, Jinan, PR China

a r t i c l e i n f o

abstract

Article history:
Received 28 November 2011
Received in revised form
10 May 2012
Accepted 11 May 2012
Available online 21 May 2012

Ethnopharmacological relevance: The resinous exudates of the Commiphora species, known as myrrh,
are used in traditional Chinese medicine for the treatment of trauma, arthritis, fractures and diseases
caused by blood stagnation. Myrrh has also been used in the Ayurvedic medical system because of its
therapeutic effects against inammatory diseases, coronary artery diseases, gynecological disease,
obesity, etc.
Aim of the review: Based on a comprehensive review of traditional uses, phytochemistry, pharmacological and toxicological data on the genus Commiphora, opportunities for the future research and
development as well as the genus therapeutic potential are analyzed.
Methods: Information on the Commiphora species was collected via electronic search (using Pubmed,
SciFinder, Scirus, Google Scholar and Web of Science) and a library search for articles published in
peer-reviewed journals. Furthermore, information also was obtained from some local books on
ethnopharmacology. This paper covers the literature, primarily pharmacological, from 2000 to the
end of December 2011.
Results: The resinous exudates from the bark of plants of the genus Commiphora are important
indigenous medicines, and have a long medicinal application for arthritis, hyperlipidemia, pain,
wounds, fractures, blood stagnation, in Ayurvedic medicine, traditional Chinese medicine and other
indigenous medical systems. Phytochemical investigation of this genus has resulted in identication of
more than 300 secondary metabolites. The isolated metabolites and crude extract have exhibited a
wide of in vitro and in vivo pharmacological effects, including antiproliferative, antioxidant, antiinammatory and antimicrobial. The bioactive steroids guggulsterones have attracted most attention
for their potent hypolipidemic effect targeting farnesoid X receptor, as well as their potent inhibitory
effects on tumor cells and anti-inammatory efciency.
Conclusions: The resins of Commiphora species have emerged as a good source of the traditional
medicines for the treatment of inammation, arthritis, obesity, microbial infection, wound, pain,
fractures, tumor and gastrointestinal diseases. The resin of C. mukul in India and that of C. molmol in
Egypt have been developed as anti-hyperlipidemia and antischistosomal agents. Pharmacological
results have validated the use of this genus in the traditional medicines. Some bioassays are difcult
to reproduce because the plant materials used have not been well identied, therefore analytical
protocol and standardization of extracts should be established prior to biological evaluation. Stem, bark
and leaf of this genus should receive more attention. Expansion of research materials would provide
more opportunities for the discovery of new bioactive principles from the genus Commiphora.
& 2012 Elsevier Ireland Ltd. All rights reserved.

Keywords:
Commiphora
Myrrh
Phytochemistry
Terpenoids
Steroids
Biological activity
Antiproliferative
Anti-inammatory
Toxicology

Abbreviations: ABTS, 2,20 -azino-di-[3-ethylbenzthiazoline sulphonate]; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; COX,
cyclooxygenase; CNS, central nervous system; DPPH, 2,2-diphenyl-1-picrylhydrazyl; FXR, farnesoid X receptor; GC, gas chromatography; HDL, high density lipoprotein;
HUVEC, human umbilical vein endothelial cells; IL, interleukin; iNOS, inducible nitric oxide synthase; JNK, c-Jun NH2-terminal kinase; LDH, lactate dehydrogenase; LDL,
low density lipoprotein; 5-LOX, 5-lipoxygenase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MIC, minimum inhibitory concentration; NO, nitric
oxide; ODC, ornithine decarboxylase; PLA2, phospholipase A2; ROS, reactive oxygen species; STAT, signal transducer and activator of transcription; SOD, superoxide
dismutase; TG, triglyceride; TID, three times a day; TNF, tumor necrosis factor; TPA, 12-O-tetradecanoylphorbol-13-acetate; VAS, visual analogue scale; VEGF, vascular
endothelial growth factor; VLDL, very-low-density lipoprotein
n
Corresponding author. Tel.: 86 531 88382012; fax: 86 531 88382019.
E-mail address: louhongxiang@sdu.edu.cn (H.-X. Lou).
0378-8741/$ - see front matter & 2012 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jep.2012.05.025

320

T. Shen et al. / Journal of Ethnopharmacology 142 (2012) 319330

Contents
1.
2.
3.

4.

5.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
Traditional uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
Phytochemical studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
3.1.
Terpenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
3.1.1.
Monoterpenoids, sesquiterpenoids and volatile oil. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
3.1.2.
Diterpenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
3.1.3.
Triterpenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
3.2.
Steroids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
3.3.
Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
Pharmacological and toxicological aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
4.1.
Anti-inammatory activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
4.2.
Analgesic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
4.3.
Inhibition of tumor-cell proliferation in vitro and in vivo. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
4.4.
Antiparasitic and antimicrobial activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
4.5.
Hepatoprotective activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
4.6.
Antioxidant activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
4.7.
Hypolipidemic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
4.8.
Hypotensive activity and cardiac protection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
4.9.
Antidiabetic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
4.10. Antiulcer activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
4.11. Miscellaneous bioactivities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
4.12. Toxicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328
Appendix ASupporting information. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328

1. Introduction
The plant resinous exudates, exemplied by frankincense,
myrrh, benzoin, Dragons blood and ferulae resina, are important
resources for traditional medicines. Their medicinal functions and
usages are recorded in the ancient literature of Egypt, Rome,
Greece, and China (Langenheim, 2003; Nanjing University of
Chinese Medicine, 2006). Myrrh, originating from Arabia, is
the exudates produced by the secretory tissue in the bark of
Commiphora species.
The genus Commiphora (Burseraceae) with more than 150 plant
species, is distributed in the tropical and subtropical regions,
especially occurring in northeastern Africa, southern Arabia and
India (Langenheim, 2003; Vollesen, 1989). The plants of Commiphora species are characterized as small trees or shrubs with
spinescent branches, pale-gray bark and reddish-brown resinous
exudates.
The resinous exudates of the genus Commiphora are commonly
used as perfume, incense, or embalming ointment, and their
medicinal values have been gradually recognized by humankind
(Langenheim, 2003). They are used in indigenous medicines for
the treatment of wound, pain, arthritis, fractures, obesity, parasitic infection and gastrointestinal diseases (Al-Harbi et al., 1997;
Zhang, 2009; Abdul-Ghani et al., 2009). Diverse secondary metabolites including terpenoids, steroids, avonoids, sugars, lignans,
etc. have been discovered in this genus (Hanus et al., 2005).
Antiproliferative, anti-inammatory, antimicrobial, hepatoprotective and cardiovascular properties of the puried metabolites and
the crude extracts have been investigated (El Ashry et al., 2003;
Shen and Lou, 2008; Deng, 2007).
The distribution of fty-one constituents and medical uses of
myrrh was reviewed by El Ashry et al (2003). A review covering
the chemical aspects of Commiphora species has appeared (Hanus
et al., 2005). Two reviews dealing with the hypolipidemic
property of guggul (the resin of Commiphora mukul) has been
published (Ulbricht et al., 2005; Sahni et al., 2005). The resin of C.
molmol mainly used in Egypt as an antiparasitic agent, its medical

use has been summarized recently (Abdul-Ghani et al., 2009;


Tonkal and Morsy, 2008). The hypolipidemic property of guggulsterones (Ramawat and Merillon, 2008) and their molecular
targets (Shishodia et al., 2008), the bioactive compounds from
the genus Commiphora and Boswellia have been reviewed
(Shen and Lou, 2008). Plant resins with antimicrobial potential
have been summarized, the resin of Commiphora species were
included (Termentzi et al., 2011). Different from the writing
objectives of above literatures, our review presents a comprehensive and up-to-date report on traditional uses, phytochemical
aspects, pharmacological functions and toxicity of this genus.
Besides, we focus on the pharmacological data reported since the
year of 2000, to provide a probable scope of future research
concerning this genus.

2. Traditional uses
Traditional uses, local names and the main pharmacological
activities of some Commiphora species from different regions are
listed in Table 1. The most frequently employed and investigated
Commiphora species are Commiphora myrrha, C. opobalsamum, C.
mukul and C. molmol. The resins of these Commiphora species
exhibit diverse therapeutic utilities, such as wound, pain, fracture,
mouth ulcer, inammatory disease, stomach disorders and microbial infection.
The recognition of the therapeutic and medicinal value of
myrrh (known as guggul in India, the resinous exudates of
C. mukul) in Ayurvedic medical system dates from 3000 years
ago. Guggul is regarded as the most important herb in the
authoritative monograph Charaka Samhita for the treatment of
obesity, and is used as a hypolipidemic agent to treat lipid disorder
(Kuppurajan et al, 1978; Singh et al., 1994; Khanna et al., 2010).
This resin is used for promoting the bone fractures union, sore
throat, mouth ulcer, wounds, skin disorders, acne, intestinal
worms, lymphadenopathy, as recorded in Bhava Prakashas

Table 1
Medicinal uses of selected Commiphora species.
Species

Regions

Local name

Traditional use

Pharmacological
activity

Extract/constituents
evaluated

Ref.

Commiphora myrrha (T. Nees) Engl.

China

Mo Yao

Skin ulcer, empyrosis, wound, fracture, oral ulcer,


toothache, pain, tumor, arthritis, inammatory diseases,
and diseases caused by blood stagnation, dysmenorrhea,
rheumatism, hemiplegia, and acroanesthesia

Antitumor
Anti-inammatory
Analgesic
Antioxidant

Shoemaker et al. (2005)


Su et al. (2011)

Wounds, worms, sepsis, cough, snakebite, infections in


mouth, teeth, and eyes
Pharyngitis, tonsillitis, gingivitis, ulcers, cough, proctitis,
sinusitis and skin inammation
Nasal congestion caused by common cold, small wounds,
and infection of the buccal cavity
Oral diseases
Sore throats, oral mucosal and gingival irritations
The same use to C. myrrha
Dyspepsia, colic, joint pain, promoting urine output,
expelling renal calculi, liver and stomach diseases

Antimicrobial

Aqueous extract
Petroleum ether
fraction
Essential oil
furanosesquiterpenoid
Ethanol and ether
extracts
Resin
Resin

Bruneton (1995)

Resin tincture
Resin tincture
Ethanol extract
Triterpenoid

Schilcher (1997)
Tyler (1993)
Al-Howiriny et al. (2005)
Shen et al. (2007)

Aqueous extract
Crude extract
Ethanol extract
Ethyl acetate extract
Tririterpenoids
diterpenoids, steroids
Crude extract
guggulipid steroids

Abdul-Ghani and Amin (1997)


Al-Howiriny et al. (2004a)
Al-Howiriny et al. (2004b)
Matsuda et al. (2004b); Francis et al.
(2004); Kimura et al. (2001); Singh
et al. (2003)
Wang et al. (2004); Ulbricht et al.
(2005); Singh et al. (1994); Szapary
et al. (2003); Ojha et al. (2008)
Panda and Kar (2005)

Greece
Britain
France

Commiphora mukul (Hook. ex Stocks) India


Engl.

Myrrh
Mo Yao
Balessan

Guggul, gugulu

Bone fracture, wound, skin disorders, inammatory


disease, arthritis, mouth ulcer, cardiovascular disease, lipid
disorder, obesity, and hypothyroidism

Antiulcer
Antiproliferative
Hypotensive
Hepatoprotective
Anti-inammatory
Anti-inammatory

Hypolipidemic

Antihypothyroidism
Antibacterial

Antidiabetic
Protecting
memory decits
Antiproliferative

Commiphora caudata Engl.

India

Commiphora berryi Engl.

India

Kilimaram, Idingil,
Kizhuvam,
Mankiluvai
Mukiluvai

Jordan
Egypt

Mor makha
Myrrh

Commiphora holtziana Engl.

Gum haggar

Analgesic Antiinammatory

Cold, fever, and wound

Gastric antiulcer
Hepatoprotective
Antioxidant

Inammation and pain


Schistosomicide, heterophycide, fasciolicide, and
molluscicide

Kill and repel tick pest populations on camel and cattle


Microbial infection

Bradley (1992)

Essential oil
chloroform extract
sesquiterpenoids
Steroids
Ethyl acetate extract

Asif Saeed and Sabir (2004)

Methanol extract
Steroids

Sharma et al. (2005); Singh et al.


(2005); Xiao and Singh (2008); Macha
et al. (2011)
Annu et al. (2010); Vikneshwaran et al.
(2008)

Ethanol extract of
leaves; Endosperm of
the seeds
Methanol extract

Antiparasitary
Antischistosomal

Stem
Commercial product
Mirazid

Antiproliferative
Antimicrobial

Aqueous suspension
Terpenoids

Analgesic
Antiectoparasitic

Sesquiterpenoids
Hexane extract

Sharma et al. (2009)


Saxena et al. (2007)

Gowri Shankar et al. (2008);


Gowrishankar et al. (2004)

Alzweiri et al. (2011)


Abdul-Ghani et al. (2009); Baghdadi
and Al-Mathal (2010); Massoud et al.
(2007); El Baz et al. (2003)
Qureshi et al. (1993)
Dolara et al. (2000); Rahman et al.
(2008)
Dolara et al. (1996)
Chikamai and Gachathi (1994)
Kokwaro (1976)

321

Commiphora confusa Vollesen

Eastern
Africa

Inammation, pain, and relieving stomach aches

Gum extract

Omer et al. (2011)

T. Shen et al. / Journal of Ethnopharmacology 142 (2012) 319330

Commiphora opobalsamum (L.) Engl.

Germany
America
China
Saudi
Arabia

Racine and Auffray (2005)

Seed decoction
Resin
Hexane extract

Essential oil

Anti-tick

Antibacterial

Expelling tapeworms
Wound
Skin infection, and ailments caused by ticks

Wound

Asres et al. (1998)

McGufn et al. (2000)


Grade et al. (2009)
Carroll et al. (1989)

Methanol extract
Resin
Malaria
Eyes painful red

Claeson et al. (1991); El Ashry et al.


(2003)
Koch et al. (2005)
Grade et al. (2009)
Smooth muscle
relaxing effect
Antimalarial
Stomach complains, wounds, and diarrhea

Materia Medica (Murthy, 1998). It is also used for the treatment of


inammatory diseases, arthritis and pain in India (Ding and
Staudinger, 2005; Singh et al., 2003). The resin of C. molmol is
now sold as an antiparasitic agent sold in the market with a
commercial name of Mirazid in Egypt (Abdul-Ghani et al., 2009).
Myrrh is used in the Arab medicine for the treatment of inammation related diseases and stomach diseases (Al-Harbi et al.,
1997).
Myrrh in China is used since the Tang Dynasty in 600 AD, and
this has been recorded in the Chinese medical document Hai Yao
Ben Cao. Myrrh used in China is the resin of C. myrrha or
C. opobalsamum. It is prescribed together with frankincense for
the treatment of pain, swelling, trauma, arthritis and fractures
(Zhang, 2009). It is widely used in dermatology to treat skin ulcer,
empyrosis and sore (Dai et al., 2001; Shang and Lu, 2007).
Medicinal applications of myrrh for trauma, arthritis, fractures
and tumors originate from its abilities of breaking up congealed
blood and promoting the blood circulation (Yifang, 2002; State
Administration of Traditional Chinese Medicine, 1996). China has
turned into the largest myrrh-importing country of the world,
most of which is for medicinal consumption (Coppen, 1995).

3. Phytochemical studies
More than 300 molecules have been identied from this genus.
The information of isolated metabolites has been provided by El
Ashry et al. (2003) and Hanus et al. (2005), introduced from the
points of plant origin and species. In present review important
phytochemical regularities and ndings since 2005 of this genus
are introduced. A comprehensive summary of structures and
resources of metabolites classied by structural types was given
in Supplementary Data.
With respect to phytochemical aspects of this genus, the
characteristics as follows deserve our full attention. (i) Terpenoids
especially the sesqui- and triterpenoids are the most abundant
constituents in this genus. (ii) The species of C. myrrha, C. mukul,
C. molmol, C. kua and C. confusa have received more phytochemical attention. (iii) The resinous exudates of Commiphora species
are dispensed on prescription in the indigenous medicines of
China, India, Egypt, etc. Therefore, the resins but not the leaves,
barks and stems of this genus, are the most commonly investigated targets for discovering bioactive compounds.

Ekadeli
Agarsu, hagar

Osilalei
Ekadeli

3.1. Terpenoids

Commiphora schimperi (O. Berg) Engl. Kenya


Commiphora habessinica (O.Berg)
Uganda
Engl.
Commiphora africana (A. Rich.) Engl. Nigeria
Uganda
Commiphora erythraea (Ehrenb.)
Ethiopia
Engl.
Commiphora tenuis Vollesen
Ethiopia

Commiphora guidottii Chiov. ex Guid. Somalia

Commiphora merkeri Engl.

Commiphora harveyi (Engl.) Engl.

Commiphora erlangeriana Engl.

Sesquiterpenoids

Fourie and Snyckers. (1989)


Anti-inammatory Triterpenoid
Infection

Sebrabaskanniedood
Zebra-bark,
corkwood
Habakhadi

Watt and Breyer-Brandwijk (1962);


Suleiman et al. (2010)
Leaf extract
antimicrobial
Wounds, anthelmintic agent, and snakebite
Umbangandlala
Umnumbi

Habtemariam (2003)
Lignans
Antitumor
Arrow poison

Kokwaro (1976)
Snakebite, gonorrhoea, and stomach disorders

Lolowi, Warab-Reb,
Rahan-Reb
Dhunkal

Eastern
Africa
Eastern
Africa
Eastern
Africa
Southern
and
Eastern
Africa
Southern
Africa
Commiphora kua Vollesen

Species

Table 1 (continued )

Regions

Local name

Traditional use

Ref.
Extract/constituents
evaluated

T. Shen et al. / Journal of Ethnopharmacology 142 (2012) 319330

Pharmacological
activity

322

3.1.1. Monoterpenoids, sesquiterpenoids and volatile oil


Monoterpenoids mainly occur in volatile oil, and identied by
gas chromatography (GC)-based techniques. Many papers have
described the GC analysis of volatile oil from different Commiphora species, covering C. myrrha (Dekebo et al., 2002a; MortezaSemnani and Saeedi, 2003), C. guidottii (Craveiro et al., 1983),
C. quadricincta (Assad et al., 1997), C. holtziana (Provan et al.,
1987; Dekebo et al., 2002a), C. sphaerocarpa and C. kataf (Dekebo
et al., 2002a). Monoterpenoids including a-pinene, camphene,
b-pinene, myrcene and limonene have been detected. It was
observed that the composition of volatile oil from different
Commiphora species varies largely. Sesquiterpenoids with low
degree of oxidation play a dominant role in volatile oil.
b-Elemene, a-copaene, a-humulene, b-selinene and germacrene
B are widely distributed sesquiterpenoids in the volatile oil of
different Commiphora species.
Fig. 1 The structures of sesquiterpenoids from the genus
Commiphora are mainly classied into germacrane, eudesmane,
guaiane, cadinane, elemane, bisabolane and oplopane groups. The
presence of furanosesquiterpenoids is characteristics of this genus.

T. Shen et al. / Journal of Ethnopharmacology 142 (2012) 319330

323

Fig. 1. Chemical structures of typical constituents isolated from Commiphora species.

More than twenty furanosesquiterpenoids covering furanogermacrane, furanoeudesmanes, furanoguaiane, furanocadinane and furanoelemane have been discovered (Table S1 and Fig. S1), since the

rst isolation of furanosesquiterpenoid from C. molmol (Brieskorn


and Noble, 1980). The discovery of sesquiterpenoid lactones,
identied to be germacranolide (1), eudesmanolides (2 and 3),

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T. Shen et al. / Journal of Ethnopharmacology 142 (2012) 319330

elemanolide (4), guaianolide (5), and cadinanolide (6 and 7) from


the resin of C. opobalsamum and C. myrrha, is the major phytochemical advance of this genus in recent years (Shen et al., 2007,
2008a, 2009; Xu et al., 2011a,b).
3.1.2. Diterpenoids
Diterpenoids mainly exist in the resin of C. mukul. The rst
diterpenoid is camphorene from the essential oil of C. mukul in
1950 (Bhati, 1950). Cembrane diterpenoids and verticillane diterpenoids are also present in the same species (Table S2). Recently,
a pimarane diterpenoid sandaracopimaric acid (8) and two
abietane diterpenoids abietic acid (9) and dehydroabietic acid
(10) have been reported from C. myrrha (Su et al., 2009).
3.1.3. Triterpenoids
Triterpenoids are major constituents isolated from Commiphora
species, covering dammarane, polypodane, octanordammarane,
cycloartane, oleanane, lupane, ursane, and lanostane (Table S3
and Fig. S3). Dammarane triterpenoids constitute the biggest group
of Commiphora triterpenoids, and more than twenty-one dammarane triterpenoids have been found in the resins of four Commiphora
species, including C. kua (Dekebo et al, 2002b; Manguro et al.,
2003a), C. dalzieli (Waterman and Ampofo, 1985), C. confuse
(Dekebo et al., 2002b; Manguro et al., 2003b) and C. myrrha
(Shen et al., 2009). Polypodane triterpenoids from this genus are
only discovered in the species of C. mukul (Kimura et al, 2001;
Matsuda et al, 2004a,b). Recently, ten cycloartane triterpenoids
(11-20) with novel substitution at C-2 position have been isolated
from C. opobalsamum and C. myrrha (Shen et al, 2007, 2008b; Su
et al., 2009).
3.2. Steroids
The steroids with eleven pregnane steroids and nine cholestane
steroids are only found in the species of C. mukul (Table S4 and
Fig. S4). Two C21 steroid isomers Z- and E-guggulsterones (21 and
22) from the resin of C. mukul (Patil et al., 1972), have attracted
lots of interest for their potent antitumor, anti-inammatory and
hypolipidemic properties (Ramawat and Merillon, 2008; Shishodia
et al., 2008).
3.3. Miscellaneous
In Commiphora species, many other secondary metabolites are
encountered such as carbohydrates, avonoids, lignans and long
chain aliphatic derivatives (Table S5 and Fig. S5). Carbohydrates
have been reported from the gum of Commiphora, and commonly
exist in the form of polysaccharide (Hough et al., 1952; Jones and
Nunn, 1955; Bose and Gupta, 1964). Acid hydrolysis of the gum
produces mono- or di- saccharides. The avonoids of this genus are
found in the ower, stem and bark, but not obtained in the resinous
exudates. 1,2,3,4-tetrahydroxy long chain aliphatic derivatives occur
in the gum, for instance, D-xylo-guggultetrol-18 and guggultetrol-20
(Patil et al., 1973), which commonly exist in the form of ferrulic acid
ester or glycoside (Zhu et al, 2001; Shen et al., 2007).

4. Pharmacological and toxicological aspects


4.1. Anti-inammatory activity
The resin of C. mukul, known as guggul in Ayurvedic medicine, has been used for the therapy of arthritis for centuries.
A clinical study indicated that the resin extract of C. mukul had
signicant improvements of osteoarthritis when treated with a
dose of 500 mg TID for 1 month (Singh et al., 2003).

The MeOH resin extract of C. mukul demonstrated signicant


inhibition of NO formation in lipopolysaccharide (LPS)-activated
murine macrophages with an IC50 value of about 15 mg/mL
(Meselhy, 2003; Matsuda et al., 2004a). Anti-inammatory
mechanism of MeOH extract against LPS-induced inammation
has been reported recently (Cheng et al., 2011). Cembrane
diterpenoids, polypodane triterpenoids, steroids and lignans isolated from this species have been tested for their NO production
and COX inhibitory activities. Z- and E-guggulsterones (21 and
22), myrrhanol A (23) and myrrhanone A (24) prevented NO
production with IC50 values of 1.1, 3.3, 21.1 and 42.3 mM,
respectively (Meselhy, 2003). Myrrhanol A (23) and mukulol
(25) inhibited the induction of inducible nitric oxide synthase
(iNOS) in LPS-activated mouse peritoneal macrophages (Matsuda
et al., 2004a). Concerning the COX inhibitory effect, cembrene
(26) and E-guggulsterone (22) are most active, with 79% and 67%
inhibition against COX-1, and with 83% and 54% inhibition against
COX-2 at 100 ppm (Francis et al., 2004).
Z- and E-guggulsterones (21 and 22) have been found to exert
their anti-inammatory properties by suppressing activation of
NF-kB and expression of NF-kB-regulated gene products
(Shishodia and Aggarwal, 2004; Lv et al., 2008). An in vivo study
accounts for anti-uveitis property of 21 and 22 has been carried
out using Lewis rats. The results showed that 21 and 22 decreased
the level of inammatory markers, such as MMP-2, NO and PGE2,
and prevented the expression of inammation related protein in
eye tissues (Kalariya et al., 2010).
Kimura et al. (2001) have studied anti-inammatory activity of
23, 24 and the resin extract of C. mukul using adjuvant-induced
air pouch granuloma model. 23 exhibited 7.9, 5.0 and 3.6 times
more potent activities on carmine content, granuloma weight and
pouch uid weight than the control drug hydrocortisone, and it
has a potential to be developed as an anti-inammatory agent.
The EtOAc resin extract of C. mukul signicantly prevented the
LPS-induced nitrite release, ROS generation, and down-regulated
the expression of COX-2, glial brillary protein and TNF-a in rat
astrocytoma cells, suggesting its potential use on neuron-inammation associated conditions in CNS disorders (Niranjan et al.,
2010). The resin extract of C. mukul and guggulsterol exhibited
inhibitory effect of MAPK, and down regulation of some inammatory mediators such as TNF-a, IL-1b and IL-2 in peripheral
blood mononuclear cells. It prompted that C. mukul and its
metabolites might exert their anti-inammatory property by
inhibiting MAPK which regulates a variety of inammation
related genes (Manjula et al., 2006).
The extracts of C. molmol and C. pyracanthoides have been
evaluated for their anti-inammatory properties. The volatile oil
of C. molmol was shown to inhibit the production of IL-1bstimulated IL-6 and IL-8 in human gingival broblasts cells
(Tipton et al., 2003). The petroleum ether extract of C. molmol
resin showed inhibitory activity against carrageenan induced
inammation and cotton pellet granuloma (Tariq et al., 1985).
Ten Commiphora species were evaluated for their anti-inammatory activity using a 5-lipoxygenase (5-LOX) assay, and the stem
extract of C. pyracanthoides was most active with IC50 of 27.86 mg/
mL (Paraskeva et al., 2008). The petroleum ether bark extract of C.
berryi and the puried friedelin showed soybean lipoxygenase
inhibitory effects with IC50 values of 15.3 mg/mL and 35.8 mM
(Kumari et al., 2011b).
The hexane extract of C. erythraea resin inhibited edematous
response with 84% reduction at a dose of 1000 mg/cm2 in croton
oil-induced mice ear edema assay. Myrrhone (27), rel-3R-methoxy-4S-furanogermacra-1E,10(15)-dien-6-one (28) and rel-2Rmethoxy-4R-furanogermacr-1(10)E-en-6-one (29) isolated from
this extract might be responsible for the antiedematous effect
(Fraternale et al., 2011). Oral administration of the ethanol leaf

T. Shen et al. / Journal of Ethnopharmacology 142 (2012) 319330

extracts of C. caudata at a dose of 250 mg/kg, inhibited 67% the


carrageenan-induced paw oedema response in rat (Annu et al.,
2010). The anti-inammatory effects of mansumbinoic acid (30)
and 2a,3b,23-trihydroxyolean-12-ene (31) have been veried
in vivo (Duwiejua et al., 1993; Fourie and Snyckers, 1989).
As summarized above, the resin of C. mukul is most frequently
investigated, and displays evident anti-inammatory properties
in vitro and in vivo, which validates its traditional use in
Ayurvedic medicine. Steroids (especially 21 and 22) and triterpenoids (23 and 24) are the anti-inammatory substances of
C. mukul. The mechanism of action related to multiple inammation-related proteins and signal pathways have been discussed,
and COX, NO formation, ROS, TNF-a, PGE2, NF-kB and MAPK have
been veried as potential anti-inammatory targets.
4.2. Analgesic activity
The 85% EtOH extract (EE) and petroleum ether fraction (PEE) of C.
myrrha displayed signicant inhibitory effect of acetic acid-induced
writhes, while not active in the hot plate assay. This result suggested
that the analgesic activity of above samples might be mediated via
peripheral pathways, but not a central one. Ethyl acetate fraction
together with EE and PEE exerted analgesic effects though decreasing
PGE2 level in formalin induced pain model (Su et al., 2011). Rats
pretreated with 10% suspension of C. molmol resin, curzarene (32) or
furanoeudesma-1,3-diene (33) increased the licking latency in a hot
plate test. 33 reduced the number of writhes caused by intraperitoneal administration of acetic acid. The analgesic effects of 32 and
33 were reversed by naloxone, indicating this analgesic activity was
exerted by an interaction with brain opioid mechanism (Dolara et al,
1996). The ethanol leaf extract of C. caudata inhibited 73.44% writhing
response at a dose of 250 mg/kg in acetic acid induced mice writhing
model (Annu et al, 2010). The analgesic activity of Commiphora
extract and pure compounds supported the use of myrrh for wound,
pain and bone fracture in indigenous medicines.
4.3. Inhibition of tumor-cell proliferation in vitro and in vivo
The crude extracts of different Commiphora species, dealing
with C. myrrha, C. molmol, and C. mukul, have been investigated
for their antiproliferative properties against tumor cells.
Shoemaker et al. (2005) reported the inhibitory effects of the
aqueous extract of C. myrrha resin against eight tumor cell lines.
The volatile oil of C. molmol decreased the cell viability of human
gingival broblasts and epithelial cells at concentrations of above
0.0025% and 0.001% (Tipton et al., 2003). The resin of C. molmol
exhibited antitumor activity in Ehrlich-solid-tumor-bearing mice
in vivo. With treatment at dose of 250 and 500 mg/kg/d, its
antitumor property was comparable to the standard drug cyclophosphamide (Al-Harbi et al., 1994). The MeOH extract of C.
mukul resin prevented benzoyl peroxide and ultraviolet light
induced skin tumor promotion in Swiss mice (Sharma et al.,
2005). Ten Commiphora species collected in South Africa were
evaluated for antiproliferative activities against human colonic
adenocarcinoma HT-29, human breast adenocarcinoma MCF-7
and human glioblastoma SF-268 cell lines. The plant materials
were extracted by CH3OH-CHCl3 (1:1). The leaf and stem extracts
of C. glandulosa were most active against HT-29 cell with IC50
values of about 50 mg/mL. While the leaf extract of C. africana
exhibited highest inhibitory effect against MCF-7, with an inhibitory rate of 53% at 100 mg/mL (Paraskeva et al., 2008).
Guggulsterones (21 and 22) inhibited the proliferation of a
wide variety of human tumor cell lines, including leukemia,
multiple myeloma, head and neck carcinoma, lung carcinoma,
melanoma, breast carcinoma, ovarian carcinoma and kidney
cancer. They were also active against gleevec-resistant leukemia,

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dexamethasone-resistant multiple myeloma and doxorubicinresistant breast cancer cells (Shishodia et al., 2007). The suppression of cell proliferation was completed by the inhibition of DNA
synthesis and cell cycle arrest in S-phase. The induced apoptosis
property of 21 and 22 has been detected through the activation of
JNK, suppression of Akt and down-regulation of anti-apoptotic
protein expression. 21 was able to inhibit the growth PC-3 and
LNCaP cells by inducing apoptosis (Singh et al., 2005, 2007).
Further study showed that its anti-prostate property was
mediated by Bax and Bak, reactive oxygen intermediate-dependent activation of JNK, and inhibition of androgen receptor
promoter activity. Later, it was reported that 21 was an inhibitor
of angiogenesis. It showed inhibition on the capillary-like tube
formation in HUVEC cells, and migration in HUVEC and DU145
cells by suppressing the secretion of proangiogenic growth
factors. This effect was conrmed by decrease in tumor burden,
microvessel area and VEGF-R2 protein expression in male nude
mice (Xiao and Singh, 2008). Pretreatment of 21 at a dose of
1.6 mM per mouse signicantly inhibited the skin edema and
hyperplasia in TPA-induced mouse skin tumorigenesis model. 21
also reduced tumor incidence, lowered tumor body burden, and
delayed tumor appearance in SENCAR mouse skin tumorigenesis
model (Sarfaraz et al., 2008). In addition, 21 prevented the
smokeless tobacco and nicotine-induced head and neck squamous cell carcinoma by inhibiting the activation of NF-kB pathway and STAT3 pathway (Macha et al., 2011; Leeman-Neill et al.,
2009). As an inhibitor of NF-kB activation, it could suppress
RANKL and tumor cell-induced osteoclastogenesis, which was
correlated with NF-kB activation (Ichikawa and Aggarwal, 2006).
The cytotoxicities of erlangerins AD were tested against two
human cells HeLa and EAhy926, and two murine cells L929 and
RAW 264.7. Erlangerins C and D demonstrated potent cytotoxicities, even comparable with the control podophyllotoxin
(Habtemariam, 2003). Picropolygamain and lupeol exhibited
cytotoxicities against human brosarcoma HT1080 cells with
EC50 values of 1.9 and 16.7 mg/mL (Nakanishi et al., 2005).
A series of cycloartane-type triterpenoids (11-19) were isolated from C. opobalsamum and evaluated for their anti-prostate
tumor activity against PC3 and Du145 cells (Shen et al., 2007,
2008b). Cycloartan-24-ene-1a,2a,3b-triol (11) was an inhibitor of
the production of androgen receptor (AR) in LNCaP cells. Octadecane-1,2S,3S,4R-tetrol 1-O-a-L-rhamnopyranoside showed inhibitory effect against PC3 and LNCaP cells, with IC50 values of 22.1
and 23.6 mM (Shen et al., 2007). In addition, 2-methoxy5-acetoxy-furanogermacr-1(10)-en-6-one (34) and 29 exhibited
inhibitory effect against LNCaP cells by suppressing AR nuclear
translocation and/or interrupting the interaction between AR and
the coactivators ARA70 and SRC-1 (Wang et al., 2011).
The mixture of two ferrulic acid derivatives (35 and 36)
exhibited antiproliferative effect against human prostate cancer
PC3 and breast cancer MCF-7 cells. It inhibited the proliferation of
P388/MDR cells, suggesting that it might be able to overcome the
P-glycoprotein mediated drug resistance (Zhu et al, 2001). Dehydroabietic acid (10) and 34 possessed potent aromatase inhibitory
activity with IC50 values of 0.32 and 0.21 mM, while sandaracopimaric acid (8) has 44% inhibition against aromatase at 0.30 mM,
suggesting that these compounds have the potential for the
treatment of breast cancer. In addition, sandaracopimaric acid
(8), abietic acid (9) and dehydroabietic acid (10) inhibited the
proliferation of human umbilical vein endothelial cells, with IC50
values of 0.122, 0.125 and 0.069 mM (Su et al., 2009).
4.4. Antiparasitic and antimicrobial activities
Mirazid, a drug containing 300 mg puried resin extract of
C. molmol, is sold in the market as an antiparasitic drug. The resin

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extract of C. molmol as schistosomicide, fasciolicide, heterophycide, dicrocoeliasis and mollusidide have been reviewed in detail
and provided sufcient evidence for its uses as antiparasitic agent
(Abdul-Ghani et al., 2009). Subsequently, it was found that the
resin of C. molmol and Mirazid displayed therapeutic effect on
hepatic coccidiosis induced by the parasite Eimeria stiedae in
domestic rabbits (Baghdadi and Al-Mathal, 2010). In addition,
Mirazid showed therapeutic effect for Giardia lamblia infected
rats, and produced a 100% reduction of intestinal and fecal
parasitic counts (Fathy, 2011).
Not only dose the resin of this genus displays antimicrobial
potential (Termentzi et al., 2011), but also the leaf, stem and bark
are active against microorganism. Paraskeva et al. (2008) have
studied antimicrobial potential of the leaf and stem extracts of ten
Commiphora against four bacteria and two yeasts. The bark
extracts of C. berryi and C. caudata displayed good inhibition on
Pseudomonas aeruginosa (Kumari et al., 2011a). Inhibitory effects
of C. swynnertonii on bacteria and fungus have been investigated
by Bakari et al. (2011). The sesquiterpenoids epicurzerenone and
(1E)-8,12-epoxygermacra-1,7,10,11-tetraen-6-one (37) exhibited
inhibitory activity against Fusarium culmorum, Phytophtora
cryptogea and Alternaria solani (Fraternale et al., 2011). Mansumbinoic acid (30) possessed potent antibacterial activity against a
multidrug-resistant strain Staphylococcus aureus with a MIC value
of 4 mg/mL (Rahman et al., 2008). A mixture of furanodiene-6-one
(38) and 2-methoxyfuranoguaia-9-ene-8-one (39) exhibited
antibacterial and antifungal activities against Escherichia coli,
Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans, with MIC values ranging from 0.18 to 2.8 mg/mL (Dolara
et al., 2000). The CHCl3 inner bark extract of C. schimperi displayed
antimalarial activity in vitro with an IC50 value of 4.63 mg/mL
(Koch et al., 2005).
4.5. Hepatoprotective activity
The reduced glutathione, glutathione S-transferase and glutathione peroxidase activities in PbAc-intoxicated rabbit model
recovered when treated with the resin of C. molmol (Ashry et al.,
2010). Pretreatment with the resin of C. opobalsamum could
shorten the barbiturate sleeping time and replenish the nonprotein sulfhydryl of liver caused by CCl4-induced live damage
(Al-Howiriny et al., 2004a). The MeOH bark extract of C. berryi
attenuated the increased levels of AST, ALT, ALP and serum
bilirubin, activated SOD, catalase and glutathione peroxidase,
and reduced the fatty degeneration and necrosis in CCl4-induced
hepatic injury model in rats (Gowri Shankar et al., 2008).
4.6. Antioxidant activity
Singlet oxygen was an actor of lipid peroxidation and DNA
degradation, and a potential reason for the damage of cells. The
essential oil of C. myrrha exhibited potent singlet oxygen quenching activity better than the control a-tocopherol. This effect was
attributed by the reaction between furan ring of C. myrrha
constituents (particular the furanosesquiterpenoids) and singlet
oxygen (Racine and Auffray, 2005). Three furanosesquiterpenoids
(27-29) from C. myrrha showed DPPH radical scavenging activity
with EC50 values of 1.08, 4.29 and 2.56 mg/mL (Fraternale et al.,
2011).
The stem extracts of C. tenuipetiolata, C. neglecta and C. mollis
showed antioxidant activity in ABTS assay with IC50 values of
5.10, 7.28 and 8.82 mg/mL (Paraskeva et al., 2008). While the stem
extract of C. schimperi, C. neglecta, C. tenuipetiolata, C. edulis,
C. berryi and C. caudata exhibited antioxidant effect in the DPPH
assay, with IC50 values between 7.31 and 26.92 mg/mL (Paraskeva
et al., 2008; Kumari et al., 2011a).

4.7. Hypolipidemic activity


Gugulipid, a standardized resin extract of C. mukul, has been
sold in the market for the treatment of hyperlipidemia. Ulbricht
et al (2005) has summarized the hypolipidemic results of the
C. mukul resin before 2003. Herein we focused the literature
published since the previous review.
The resin of C. mukul and the active guggulsterone were
inhibitors of low density lipoprotein (LDL) oxidation, and benecial for the treatment of atherogenesis (Wang et al., 2004). It
decreased the cholesterol and triglyceride (TG) levels, and
increased the SOD activity on hypercholesterolemic rabbit model
(Khanna et al., 2010). Administration of guggulipid (50 mg twice a
day), the total cholesterol, LDL, TG, and the total cholesterol/high
density lipoprotein (HDL) ratio decreased (Singh et al., 1994). A
clinical study exhibited that gugulipid (containing 2.5% guggulsterones) increased the LDL level, but had no impact on the level
of cholesterol, HDL, TG and very-low-density lipoprotein (VLDL)
(Szapary et al., 2003). However, a conict clinical result reported
that total cholesterol and HDL content decreased signicantly
when treated by gugulipid, and no changes of LDL and TG
contents were found between the placebo and control groups
(Nohr et al, 2009). Above different results might be caused by
administration of different C. mukul materials.
There is no doubt that guggulsterones (21 and 22) are the most
potent hypolipidemic substances in the C. mukul resin (Ramawat
and Merillon, 2008). Their potent hypolipidemic property is based
on the inhibition of the farnesoid X receptor (FXR), a nuclear
hormone receptor activated by bile acids (Urizar et al., 2002). The
cembrane diterpenoids (25-26 and 40-41) and verticillane diterpenoids (42) from the same species suppressed the cholateactivated rate of human pancreatic IB phospholipase A2 (PLA2),
which controls gastrointestinal absorption of fat and cholesterol
(Yu et al., 2009). The combined hypolipidemic activities of
guggulsterones targeting on FXR and cembrane diterpenoids
targeting on PLA2 accounted for the potent hypolipidemic activity
of C. mukul resin.

4.8. Hypotensive activity and cardiac protection


Treated with the C. mukul extract, the increased heart rate and
left ventricular end diastolic pressure, decreased arterial pressure,
and altered myocardial contractility indices caused by myocardial
ischemic impairment were prevented, and the cardiac function
have been improved (Ojha et al., 2008). Intravenous administration
of aqueous branch extract of C. opobalsamum decreased systemic
arterial blood pressure and heart rate of anaesthetised rats.
This hypotensive function was exerted though the activation of
muscarinic cholinergic receptors (Abdul-Ghani and Amin, 1997).

4.9. Antidiabetic activity


Bellamkonda et al. (2011) reported antihyperglycemic and
antioxidant effects of the ethanol resin extract of C. mukul in
streptozotocin-induced diabetic rat model, which were benet for
the treatment of diabetes. As the major constituent of C. mukul
resin, guggulsterones (21 and 22) prevented the impairment of
glucose-stimulated insulin secretion, and protected the normal
physiological function of pancreatic b cells (Lv et al., 2008).
A depth in vivo study revealed that 21 and 22 reduced the level
of the blood glucose and plasma insulin, and increased the
glycogen content in high fat diet induced type II diabetic models.
The function of G6Pase, an important antidiabetic target, has been
interfered by 21 and 22 (Sharma et al., 2009).

T. Shen et al. / Journal of Ethnopharmacology 142 (2012) 319330

4.10. Antiulcer activity


The aqueous extract of C. molmol resin provided dose-dependent anti-ulcer and gastric mucosa protective effects in 80%
ethanol, NaCl, NaOH and indomethacin induced ulcer model in
rats. The necrosis, erosion, congestion and haemorrhage of the
stomach wall caused by 80% ethanol were improved by pretreatment with C. molmol extract (Al-Harbi et al., 1997). The resin
extracts of C. opobalsamum and C. berryi displayed similar
protective effects in different mice ulcer models (Al-Howiriny
et al., 2005; Gowrishankar et al., 2004). These data are consistent
with its use for treatment of stomach diseases in traditional
medicines.
4.11. Miscellaneous bioactivities
The resin of C. mukul ameliorated 6-n-propyl-2-thiouracil
induced hypothyroidism in female mice model. The values of
lipid peroxidation decreased, while SOD and catalase activities
increased by treating with the resin extract of C. mukul at a dose
of 200 mg/kg/d (Panda and Kar, 2005). Z-guggulsterone (21), the
bioactive constituent of the C. mukul resin, increased the iodineuptake by thyroid, and enhanced the thyroid peroxidase and
protease activity in vivo (Tripathi et al., 1984).
T-cadinol (43) from the resin of C. guidottii exhibited smooth
muscle relaxing effect on the isolated guinea pig ileum and an
inhibition on cholera toxin-induced intestinal hypersecretion
in mice (Claeson et al, 1991). 4(15)-eudesmene-1b,6a-diol (44),
(-)-oplopanone (45), and 6b,10b-dihydroxy-4(15)-guaiene (46)
from the same species displayed smooth muscle-relaxing properties, but weaker than T-cadinol (Andersson et al., 1997).
Saxena et al. (2007) reported that the EtOAc extract of C. mukul
resin had signicant protection for streptozotocin-induced memory decit in rat because of its acetylcholinesterase inhibitory and
antioxidant properties. A series of sesquiterpenoids from C.
myrrha showed neuroprotective effects against MPP -induced
neuronal cell death in H-SY5Y cells (Xu et al., 2011a,b). A mixture
of 38 and 39 possessed anaesthetic activity by blocking the
inward sodium current of excitable mammalian membranes
(Dolara et al., 2000).
4.12. Toxicity
A goat was poisoned and eventually died from the oral
administration of C. myrrha resin at a dose of 15 g/kg/d. The
safe dose of the resin was suggested to be 0.25 /kg/d (Omer and
Adam, 1999). Side effects of the extract of C. mukul resin have
been observed including mild gastrointestinal discomfort, possible thyroid problems and generalized skin rash (Nohr et al., 2009).
The volatile oil of myrrh has pungent for skin, respiratory and
digestive systems, and leading to allergy, nausea and decrease in
locomotor activity (Li et al., 2008; Rao et al., 2001). That is the
reason why myrrh is pre-treated with heat to reduce the volatile
oil content before prescription in traditional Chinese medicine
(Chen et al., 2010; Zhang and Zhu, 2005). The resin of
C. erlangeriana is poisonous to humans and animals, and used
for arrow poison in Eastern Africa (Habtemariam, 2003).

5. Conclusions
The present review discusses the phytochemical and pharmacological aspects of the genus Commiphora, and especially provides a detailed analysis of the literature published since the year
of 2000. Terpenoids were regard as the major constituents in this
genus, while avonoids and lignans commonly occurred in the

327

bark or stem. Steroids and polypodane triterpenoids, characteristically present in the resin of C. mukul, might be important
chemtaxonomic markers to identify Commiphora plant species
from the phytochemical point of view.
Pharmacological studies carried out on crude extracts and pure
metabolites provided pragmatic documents for its traditional
uses, and have revealed this genus to be a valuable source for
medicinally important molecules. Regarding the constituents
contributed to medicinal values, the ndings indicated that
triterpenoids and diterpenoids are mainly responsible for antiinammatory property, sesquiterpenoids for antimicrobial,
smooth muscle-relaxing and analgesic effects, lignans for the
cytotoxic and toxicity, and steroids for antiproliferative, antiinammatory, hypolipidemic and antidiabetic activities. Guggulsterones (21 and 22) displayed potent inhibitory effect on tumor
cells in vitro and in vivo, as well as anti-inammatory property
in vivo. Myrrhanol A (23), a polypodane triterpenoid from C.
mukul, exhibited more potent anti-inammatory effect than
hydrocortisone in adjuvant-induced air pouch granuloma model.
Hence, 21, 22 and 23 have the potential to be developed as
antitumor and anti-inammatory agents. Above three compounds
only occur in the resin of C. mukul, and this nding supports its
traditional uses in Ayurvedic medicine as an anti-inammatory
agent.
Throughout our literature review we observed that different
Commiphora species were inclined to dissimilar pharmacological
functions. The resin of C. mukul possesses potent anti-inammatory and hypolipidemic effects targeting cardiovascular diseases,
and has been developed as hypolipidemic agent. The resin of
C. molmol is good at the treatment of ulcer and diseases induced
by microbial infections, its crude extract has been sold in the
market as an antiparasitic drug. The resin extracts of C. opobalsamum and C. berryi exhibit protection on ulcer and hepatotoxicity
in mice. The resin of C. myrrha is expertized in relieving the pain.
These outcomes validate the ethnopharmacological uses of Commiphora species in different regions, however, a serious aw
exists in the pharmacological studies. Most of the plant material
used in above bioassay was not well characterized, and this defect
led to the difculty to reproduce the reported results. To add the
availability of primary experimental data, identication and
quantitation of bioactive substances and standardization of
extracts are conducted prior to the pharmacological test.
The toxicity of Commiphora species is limited, mainly involving
in the allergy, nausea and decrease of locomotor ability attributed
by volatile oil. The resin of C. erlangeriana is a more toxic material
because it contains lignans poisonous to human.
In order to further develop the medical uses of Commiphora
species some research questions need to be addressed. Former
research of this genus focused on the resinous exudates, and other
plant tissue should be paid more attention, for example, stem,
bark and leaf. Expansion of research materials would provide
more chances for discovery of new bioactive principle from the
genus Commiphora. Validating the correlations of the ethnomedical uses, bioactive substances and pharmacological effects is of
special importance, and is still the primary task for future
research. Efforts are also needed to detailedly investigate the
physiological and biochemical functions demonstrated by these
species, identify the individual bioactive natural products, and
illustrate their mechanism of action. The current results are
largely limited to in vitro bioassay, and in vivo studies using
laboratory animals are needed. Furthermore, the promising
results conrmed by animal models should be further investigated by clinical trials. Suitable analytical and standardization
protocols of plant materials should be developed, since these are
the groundwork for convincing and reproducible pharmacological
studies.

328

T. Shen et al. / Journal of Ethnopharmacology 142 (2012) 319330

Acknowledgments
This work was nancially supported by NNSFC (No. 81001376),
GIIFSDU, China Postdoctoral Science Foundation (No.201104602
and 20100471536), and Postdoctoral Innovation Foundation of
Shandong Province (No. 201002018).

Appendix A. Supporting information


Supplementary data associated with this article can be found in
the online version at http://dx.doi.org/10.1016/j.jep.2012.05.025.

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