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Hepatoprotective properties of Commiphora opobalsamum ("Balessan"), a traditional medicinal plant of Saudi Arabia


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The hepatoprotective activity of an ethanolic extract of Commiphora opobalsamum ("Balessan") was investigated in rats by inducing hepatotoxicity with carbon tetrachloride:liquid paraffin (1:1). This extract has been shown to possess significant protective effect by lowering serum transaminase levels (serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase), alkaline phosphatase and bilirubin. Pretreatment with an extract of Balessan prevented the prolongation of the barbiturate sleeping time associated with carbon tetrachloride-induced liver damage in mice. On the other hand, CCl4-induced low-level nonprotein sulfhydryl concentration in the liver was replenished by the Balessan extract. These data suggest that the plant C. opobalsamum may act as an antioxidant agent and may have a hepatoprotective effect.
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DRUGS EXPTL. CLIN. RES. XXX(5/6) 213-220 (2004)
1) Medicinal, Aromatic and Poisonous Plants Research Center (MAPPRC), College of Pharmacy, King Saud
University, Saudi Arabia.
2) Department of Pathology, College of Medicine, King Khalid University Hospital, King Saud University, Saudi
Summary: The hepatoprotective activity of an ethanolic extract of Commiphora opobalsamum ("Balessan")
was investigated in rats by inducing hepatotoxicity with carbon tetrachloride:liquid paraffin (1:1). This extract has
been shown to possess significant protective effect by lowering serum transaminase levels (serum glutamate
oxaloacetate transaminase and serum glutamate pyruvate transaminase), alkaline phosphatase and bilirubin.
Pretreatment with an extract of Balessan prevented the prolongation of the barbiturate sleeping time associat-
ed with carbon tetrachloride-induced liver damage in mice. On the other hand, CO
/induced low-level nonpro-
tein sulfhydryl concentration in the liver was replenished by the Balessan extract. These data suggest that the
plant C. opobalsamum may act as an antioxidant agent and may have a hepatoprotective effect.
Balessan is the Arabic or local name of Commi-
phora opobalsamum (L.) Engl., family Burseraceae.
This plant is one the most ancient plants, with a mag-
Address for correspondence: S. Rafatullah, Medicinal, Aro-
matic and Poisonous Plants Research Center (MAPPRC),
College of Pharmacy, King Saud University, RO. Box 2457,
Riyadh 11451, Saudi Arabia.
Fax: 00966-1-467-6383 E-mail:
nificent history of healing, and was a valuable medic-
inal agent in ancient Arabia. It grows wild in countries
on both sides of the Red Sea (1). It has been used in
diseases of liver, stomach and urinary tract. A decoc-
tion or tincture is used by local traditional healers for
the treatment of chest, stomach and kidney com-
plaints; to promote digestion; and to relieve rheuma-
tism, scurvy and jaundice (2). Abdul-Ghani and Amin
(3) have reported an antihypertensive activity of an
aqueous extract of this plant in rats. However, there is
0378-6501/2004/5/6 00213+7 $02.50/0
© 2004 Bioscience Ediprint Inc.
Al-Howiriny T.A. et al.
a dearth of scientific data on this plant and therefore
the present investigation was undertaken to evaluate
the antihepatotoxic potential of an ethanolic extract in
laboratory animals.
Materials and methods
Plant collection and extraction. The aerial parts of
the plant were collected from the Farasan Island of
the Red Sea (Saudi Arabia) in March 2002 and were
identified by our taxonomist Dr. Atiqur Rahman (Col-
lege of Pharmacy, King Saud University). A voucher
specimen (#14312) was deposited at the herbarium
of the College of Pharmacy for future reference. Pow-
dered shade-dried aerial parts of the plants were
macerated in 96% ethanol for 36 h. Solvent elimina-
tion was carried out under reduced pressure which
yielded a brownish semisolid compound. A solution
of the extract was made in distilled water for admin-
istration to animals.
Animals. Wistar albino rats, of either sex and ap-
proximately the same age (8-10 weeks), weighing
180-200 g, obtained from the Experimental Animal
Care Center, College of Pharmacy, King Saud Uni-
versity, Riyadh, were used. Swiss albino mice were used
for studies of sleeping time. The animals were kept in
constant temperature (22 ± 2 °C), humidity (55%)
and light-dark conditions (12/12 h light/dark ratio). The
animals were provided with Purina chow and free ac-
cess to drinking water ad libitum.
Phytochemical screening. A phytochemical anal-
ysis of the aerial parts of Balessan was conducted for
the detection of alkaloids, cardiac glycosides, flavo-
noids, tannins, anthraquinones, saponins, volatile oil
and cyanogenic glycosides, glucosinolates, coumarins,
sterol and/or triterpenes (4).
Induction of acute hepatotaxicity by carbon tetra-
chloride (COJ. Male Wistar rats were divided into four
groups containing six animals in each group. Group I
was kept as a control group. Groups II, III and IV re-
ceived 0.25 ml of CCI
in liquid paraffin (1:1) per 100 g
body weight intraperitoneally (5). Group II received
only CCI
treatment. Groups III and IV were treated
with 250 and 500 mg/kg of ethanolic extract of
Balessan, respectively. Drug treatment was started 5
days prior to CCI
administration and continued until
the end of the experiment. After 48 h, following CCI
administration, animals were sacrificed using ether
anesthesia. Blood was collected by heart puncture
and the serum was separated. The liver was immedi-
ately removed and a small piece was fixed in 10%
formalin for histopathological assessment.
Assay of serum glutamic-oxaloacetic transaminase
(GOT), glutamic-pyruvate transaminase (GPT), alka-
line phosphatase (ALP) and total bilirubin activities.
The collected blood was centrifuged at 3,000 rpm for
10 min to separate the plasma. The plasma was ana-
lyzed for the biochemical parameters including GOT,
GPT, alkaline phosphatase and total bilirubin (6, 7).
Estimation of nonprotein sulfhydryl groups (NP-SH).
The activity of NP-SH was measured according to the
method of Sedlak and Lindsay (8). The liver tissue was
homogenized in ice-cold 0.02 M ethylenediaminete-
traacetic acid (EDTA). Aliquots of 5 ml of the homo-
genates were mixed in 15 ml test tubes with 4 ml of
distilled water and 1 ml of 50% trichloroacetic acid.
The tubes were shaken intermittently for 10-15 min and
centrifuged at 3,000 g. Two milliliters of supernatant
were mixed with 4 ml of 0.4 M Tris buffer, pH 8.9, and
0.1 ml of 0.4% (5,5-dithio-bis- [2-nitrobenzoic acid])
(DTNB) was added and the sample was shaken. The
absorbance was read within 5 min of addition of DTNB
at 412 nm against a reagent blank with no homo-
Hepatoprotective properties of Balessan
Measurement of phenobarbital-induced sleeping
time. Mice were divided into four groups of 10 ani-
mals each. Group I received the vehicle (0.3 ml of
saline); group II received CCI
only. Groups III and IV
received Balessan extract (250 and 500 mg/kg orally).
Thirty minutes after the administration of the extract,
animals of groups II, III and IV were treated with sodi-
um phenobarbital (50 mg/kg, intraperitoneally). The
time interval between the onset and the regaining of
the righting reflex was measured as sleeping time (9).
Histopathalogical studies. The liver tissue was fixed
in 10% ethanol buffered formalin and processed through
graded ethanol, xylene and impregnated with paraf-
fin wax; sections were made by microtome. After stain-
ing with hematoxylin-eosin stain, the sections were
examined under a research microscope by a person
who was not aware of the experimental protocols. The
different histopathological indices were screened (10).
Statistical analysis. The data were statistically ana-
lyzed using Student's f-test.
The preliminary qualitative phytochemical screen-
ing of aerial parts of Balessan revealed the presence
of flavonoids, tannins, sterols and/or triterpenes.
The effects of ethanolic extract on CCI
hepatotoxicity in rats are shown in Table I. Rats sub-
jected to the CCI
regimen alone developed signifi-
cant hepatocellular damage as evidenced by a sig-
nificant elevation in serum activities of GOT, GPT, ALP
and bilirubin concentrations compared with normal
values, which have been used as reliable markers of
hepatotoxicity. Oral administration of an ethanol extract
of Balessan (250 and 500 mg/kg) exhibited a signifi-
cant reduction in CCI
-induced increased levels of
SGOT, SGPT, ALP and serum bilirubin concentrations.
NP-SH contents in liver were significantly decreased
following the administration of CCI
. Treatment with
Balessan extract (either dose) significantly reversed
the NP-SH level (Table II).
There was a significant lowering of phenobarbital-
induced sleeping time following the administration of
the Balessan extract (500 mg/kg) in the CCI
acute liver injury model (Table III). In contrast, the lower
dose (250 mg/kg) showed an insignificant reduction
in sleeping time.
Histological observations supported the results
obtained from liver enzyme assays. Confluent hepat-
ic cell necrosis and karyorrhexis and karyolysis of
hepatocytes were also noted in the control CCI
treated rat livers. Extensive hepatic cell steatosis was
seen. No confluent necrosis was observed in either of
the groups treated with Balessan extract (Figs. 1-4).
Table I Effect of an ethanol extract of Balessan on some enzymes and bilirubin in rats with CCI
-induced liver damage
Treatment (n = 6) Dose mg/kg GOT mg/kg
GPT mg/dl ALP mg/dl Bilirubin mg%
N. saline 151.00 ± 9.76
91.4 ± 3.94 399.16 ± 46.60 0.72 ± 0.025
1.25 ml/kg
± 49.35
474.41 **"
± 35.67
± 33.65
Balessan + CCI
256.41'"" ± 13.74
123.66"'" ± 6.60
509.33*"" ± 23.06
1.45 ± 0.003
Balessan + CCI
200.08"*" ± 30.80 115.58"*" ± 9.99
489.00 """ ± 24.55
1.06"*" ± 0.03
"*p < 0.001 Student's f-test;
as compared with the control (normal saline) group; "as compared with the CCI
group. GOT = glutamic-
oxaloacetic transaminase; GPT = glutamic-pyruvate transaminase; ALP = alkaline phosphatase.
Al-Howi.riny T.A. et al.
Table II Effect of an ethanolic extract of Balessan on the level of nonprotein sulfhydryl (NP-SH) groups in the liver of rat treated with CCI
Treatment {n = 6) Dose mg/kg orally NP-SH (mean ± SE) mol/g of tissue
Control normal saline - 1.62 + 0.13
Control CCI
- 0.95 ± 0.04"'
Balessan extract + CCI
250 1.26 ± 0.008"
Balessan extract + CCI
500 1.50 ± 0.07""
As compared with the control (normal saline) group;
as compared with the control (CO.). "p < 0.01; '"p < 0.001 Student's f-test.
The efficacy of any hepatoprotective drug is
essentially dependent on its capability to either
reduce harmful effects or to maintain the normal
hepatic physiological mechanisms that have been
unbalanced by the hepatotoxin (5). The results of the
present study reveal that the ethanolic extract of
Balessan possesses significant hepatoprotective
and antioxidant activities against CCI
-induced liver
damage in rats. It has been observed that CCI
is bio-
transformed by the cytochrome P-450 system to the
trichloromethyl free radical. This free radical may
react again with oxygen to form a trichloromethyl per-
oxyl radical, which may attack lipids on the mem-
brane of endoplasmic reticulum. The trichloromethyl
peroxyl free radical leads to lipid peroxidation, the
disruption of Ca
homeostasis and, finally, results in
cell death (11,12). Therefore, leakage of large quan-
tities of enzymes into the blood stream are often
associated with massive necrosis of the liver (13).
Administration of CCI
results in a rapid increase of
serum GOT GPT and ALP levels (14). Serum GOT can
be found in the liver, cardiac muscle, kidney, brain,
pancreas, lungs, skeletal muscle, leukocytes and ery-
throcytes (in decreasing concentrations) (15), whereas
the highest concentration of Serum GPT is found in the
liver. In tissues, Serum GPT occurs in two locations,
the cytosol and mitochondria (16). Serum GPT ap-
pears to be a more sensitive and specific test of acute
hepatocellular damage than Serum GOT (14). There-
fore, the possible hepatoprotective mechanism of
Balessan extract on CCI
-induced liver injuries may be
due to the following factors: (i) inhibition of cytochrome
P-450 activity; (ii) prevention of lipid peroxidation; (iii)
stabilization of the hepatocellular membrane; and (iv)
enhancement of protein synthesis (17).
Furthermore, alkaline phosphatase (ALP) is the
prototype of these enzymes that reflects the patho-
logical alteration in biliary flow (18). CCI
-induced ele-
vation of this enzymatic activity in serum is in line with
Table III Effect of the ethanolic extract of Balessan on duration of phenobarbital sleeping time of mice treated with CCI
Treatment (n = 6) Dose mg/kg Sleeping time (mice) Reduction in sleeping time
Only phenobarbital
33.2 ± 2.33
+ phenobarbital
132.2 ± 6.15"*
+ Balessan extract + phenobarbital 250 + 50
127.8 ± 4.77
+ Balessan extract + phenobarbital 500 + 50
109.00 ± 5.12'
216 'p < 0.05, '"p < 0.001 Student's f-test.
As compared to the phenobarbital group;
as compared to the CCI + phenobarbital group.
Hepatoprotective properties of Balessan
Fig. 1 Control animal (no treatment) portal space (in the center)
surrounded by normal liver parenchymal cells. Hematoxylin-eosin
the high level of serum bilirubin content (17). The
extract-mediated suppression of the increased ALP
activity with the concurrent depletion of raised biliru-
bin level suggests the possibilities of the extract
being able to stabilize biliary dysfunction in the rat
liver, thereby indicating its effectiveness in maintain-
ing the normal functional status of the liver (20). Our
observations in the present study also indicate that
treatment with CCI
caused a significant reduction in
Fig. 2 Liver parenchyma after CCI,, treatment (exposure); central
vein of the lobule surrounded by confluent hepatic cell necrosis. Note
karyorrhexis and karyolysis of hepatocytes. Hematoxylin-eosin x 200.
NP-SH concentration in the rat liver. An ethanolic
extract of Balessan, however, offered a significant
replenishing of the NP-SH level. Thus, sulfhydryl
seems to have a role hepatoprotection through its
antioxidant potential (21, 22). Additionally, phenobar-
bitone-induced sleeping time is significantly pro-
longed in liver damage and this parameter may be
employed as a measure of functional status of the
hepatic drug-metabolizing system (23).
Al-Howiriny T.A. et al.
Fig. 3A Liver parenchyma after CCI
exposure and Balessan 250 mg/
kg treatment. No confluent necrosis is evident. Instead, the pericen-
tral area displays extensive hepatic cell steatosis as well as inflam-
matory infiltrate. Hematoxylin-eosin x 200.
Regarding the effect of CCI
on liver cells and the
protective effect of Balessan, no confluent necrosis
was observed in either Balessan extract-treated
groups, which supports our biochemical findings.
The chemical constituents of Balessan, respon-
sible for its hepatoprotective activity against chemi-
cal injury, is not known. However, Balessan contains
a number of phytochemical constituents, including
flavonoids, saponin, volatile oils, sterol and/or tri-
terpenes. All of these constituents are known to
Fig. 3B Liver parenchyma after CCI
exposure and Balessan 250
mg/kg treatment. No confluent necrosis is evident. Instead, the
pericentral area is localized around central vein. Hematoxylin-
eosin x 200.
exhibit antioxidant activity, offer protection against
cell damage and possess free radical scavenging
effects (24, 25). Interestingly, some Commiphora
species have been shown to possess diversified
activities through various mechanisms. These in-
clude Commiphora molmol and Commiphora
mukul, which showed pharmacological effects that
included anti-inflammatory, antihepatotoxic, antic-
holesterolemic, antiulcer and cytotoxic actions (26-
Hepatoprotective properties of Balessan
Fig. 4 Liver parenchyma after CCI
exposure and treatment with
500 mg/kg of Balessan extract. There is no evidence of necrosis or
bile retention. The rim of steatotic hepatocytes appeared and sur-
rounds the periportal space. Hematoxylin-eosin x 200.
In conclusion, this study demonstrates that Ba-
lessan possesses significant hepatoprotective and
antioxidant effects in rats. Further studies are neces-
sary to isolate the active chemical component(s) and
to elucidate its exact mechanism(s) of action.
The authors are grateful to the Research Center,
College of Pharmacy, KSU, grant CPRC#123, and to
Mr. Malik Sawood for his assistance.
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Diabetes mellitus is a rapidly spreading global metabolic disorder that has serious social, health, and economic consequences. Herein, we have evaluated in vivo antidiabetic and antihyperlipidemic effects of myrrhanone-B and myrrhanol-B (isolated from Commiphora mukul Hook). We observed that treatment with myrrhanone-B and myrrhanol-B at a dose of 5 and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and the concentration of blood glucose level (BGL) in alloxan (120 mg/kg) induced diabetic mice, which indicates that the compounds possess strong anti-diabetic activities. In the biochemical analysis, these compounds improved an abnormal level of total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL-C) to a normal level and increased the high-density lipoprotein cholesterol level (HDLC). Later, drug target of compounds was predicted through in-silico docking which shows that these compounds nicely fit in the active site of α-glucosidase enzyme and mediates excellent interactions with the catalytic residues, Asp214 and Asp349. The in-silico results were confirmed by in-vitro testing of myrrhanone-B and myrrhanol-B against α-glucosidase where both the compounds exhibited excellent inhibitory potency with IC50 values of 19.50 ± 0.71, and 16.11 ± 0.69 µM, respectively. Furthermore, mechanistic study was conducted to observe their binding mechanism, which reflect that myrrhanol-B has mixed type of inhibition (ki = 12.33 ± 0.030 µM), while myrrhanone-B demonstrates competitive type of inhibition (ki =14.53 ± 0.040 µM).
Full-text available
The genus Commiphora (Burseraceae) comprises about 150–200 species, most of which grow in the dry bushlands of tropical Africa and Madagascar, Arabia, India, and South America. To date, more than 300 compounds belonging to different classes of compounds have been reported from the genus, though terpenoids are the most abundant constituents. Diterpenes, sesquiterpenes, and monoterpenes were reported from different Commiphora species. These include dammarane triterpenes from C. dalzielii and C. confusa. Mansumbinones or dammarane triterpenes from C. kua, lignans, and its epimer picropolygamain were reported from the resins of C. kua and C. erlangeriana. C. myrrha, C. sphaerocarpa, C. holtziana, and C. kataf constitute monoterpenes and sesquiterpenes. Some of these compounds showed different biological activities. Ethnobotanical information gathered from local people revealed that the resins of these species enjoy a wide array of traditional uses such as human medicine, treatment for maladies of cattle, and insect repellents. In this chapter, we collected relevant information by searching three scientific databases (Web of Science, Google Scholar, Scopus), covering the time period from 1950 to 2021. The literature review revealed that the resins of Commiphora are of considerable medicinal, cultural, and economic significance; and thus, detailed research such as sustainable conservation, value addition, and preclinical and clinical studies are required for further utilization and commercialization of underutilized resins of Commiphora species. Here we review the ethnobotanical, phytochemical composition, and pharmacological activities of the resins obtained from several Commiphora species.
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Objectives Dengue infection is a serious public health problem in several regions of the world due to the lack of effective and appropriate therapy mainly for severe infection. Therefore, the development of agents with inhibitory properties targeting the dengue virus (DNV) replication is of utmost significance. Methods Guggulsterone, a sterol reported in a local medicinal tree, Commiphora gileadensis, was investigated in silico for its inhibitory potency of dengue virus. Interaction between this guggulsterone and NS5 RNA dependent RNA polymerase, dengue methyltransferase, NS3 protease-helicase, and dengue virus type 2 envelope glycoprotein were determined using molecular docking and molecular dynamics simulations study. Guggulsterone's ADME and toxicity was predicted in silico as well. Results Our data revealed that guggulsterone has the lowest docking energy (-5.5kcal/mol) with dengue NS5 RNA-dependent RNA polymerase. While the interaction of guggulsterone with dengue virus type 2 envelope glycoprotein exhibited the highest docking energy (-3.4 kcal/mol), and was the most stable complex during molecular dynamic simulation. Guggulsterone is predicted to be a probable inhibitor of dengue virus type 2 envelope glycoprotein. ADME prediction showed no violation of Lipinski and Veber rules of guggulsterone. The tested compound may inhibit CYP2C19 and CYP2C9 and cannot inhibit CYP1A2, CYP2D6, and CYP3A4. Guggulsterone was shown to have no hepatotoxicity, cytotoxicity, or mutagenicity. Conclusions It can be concluded from this study that guggulsterone may be applied as a natural compound for the prevention or treatment of dengue infections. More in vitro and in vivo testing is needed to validate the effectiveness of this natural compound.
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Commiphora species are of high medicinal importance. They are distributed in Saudi Arabia, mainly in rocky habitats and regions under mountains, including the east of Tihama, forming a distinct element of Saudi flora. The present study focuses on the botanical characterization of five species of Commiphora, i.e., C. erythraea, C. gileadensis, C. kataf, C. myrrha, and C. quadricincta. The morphological characters for each species were recorded comparatively, and their taxonomic relationships were examined using gross morphology by generating a UPGMA dendrogram, which separated the Commiphora species into two distinct groups. A dichotomous key was generated to facilitate the identification process of the plant, even by naked eye, by obvious characteristics. Because of the similarities in anatomical structure of the stem and petiole of most studied species, only the quantitative variations are illustrated comparatively. Seed macro- and micro-morphological characteristics were recorded comparatively to be used in the identification of a species in the case of leaf absence. The phytochemical study included measurements of total phenolic and flavonoid contents. The phytochemical results were correlated with the ethno-botanic survey. The traditional uses for all species were recorded using the questionnaire and open interviews method for data collecting. The results revealed that the most common Commiphora species that are traditionally used are C. myrrha and C. gileadensis. The study recommends more research on Commiphora species using more advanced techniques and tries to increase public awareness on the importance of these plants.
Three new cycloartane triterpenoids, commikuanoids A-C (1–3), together with four known compounds 4–7, were isolated from the resin of Commiphora kua. Their structures were confirmed by advanced NMR techniques such as 1D (¹H and ¹³C) and 2D (HMBC, HSQC, COSY, NOESY and NOE) and high-resolution mass spectrometry (HRMS). Five compounds (1–5) were screened for in vitro carbonic anhydrase II (CA II) inhibitory activity. All the tested compounds demonstrated significant activity against CA II with IC50 values ranging from 4.9–19.6 μM. Moreover, the binding pattern of each compound in the binding site of CA-II was predicted through in silico molecular docking approach. It was observed that compounds 2, 4, and 5 binds with the Zn ion present in the active site of CA II, while compounds 1 and 3 mediated hydrogen bonding with Thr199 of CA-II, and all the compounds showed good binding score (> − 5 kcal/mol).
Despite a large number of liver disorders, clinically useful drugs are scarce. Moreover, the available therapies are facing the challenges of efficacy and safety. Commipohora mukul has been used in folk medicine globally for millennia for the treatment of several ailments. The current study was designed to evaluate the possible hepatoprotective activity of Myrrhanone B (MN) and Myrrhanol B (ML) isolated from C. mukul using an animal model. The animals (Swiss albino mice) were segregated into seven groups, each comprising six mice. The first group was treated with normal saline at a dose of 1 ML/kg daily intraperitoneally (i.p.) for one week. The second group was treated with acetaminophen (APAP) (250 mg/kg, i.p.), it was taken as a negative control. Group 3 was used as a positive control (treated with Silymarin (100 mg/kg, i.p.)). While groups 4-7 were used as experimental groups (termed as groups II to IV), which were treated with ML and MN at a dose of 0.6 mg/kg, and 1.2 mg/kg (i.p.) for one week. Subsequently, blood serum and liver tissue samples were collected for biochemical and histopathological analysis. Both compounds significantly improved the levels of liver biomarkers including aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin, lactate dehydrogenase (LDH), and alanine transaminase (ALT) as compared to the normal saline-treated group in APAP-induced hepatotoxic mice. Moreover, both compounds significantly modulated the expression of oxidative biomarkers including superoxide dismutase (SOD), reduced glutathione (GSH), and catalase (CAT) at the same doses. Additionally, ML and MN showed a remarkable improvement in histological changes with only mild inflammation, mild hemorrhage, no necrosis, and no pyknosis as compared to the control groups. In conclusion, MN and ML exhibited significant hepatoprotective effects in the animal model used in this study.
Commiphora gileadensis is commonly used in Saudi Arabia for oral hygiene. A lack of data about its biological activity encouraged us to evaluate the antioxidant and antibacterial activities of its leaf and stem extracts. Ethanol, methanol, acetone and deionized water were tested as extraction solvents. 80% methanol gave the highest extracted concentrations of phenolic and flavonoid substances. The leaf and stem extracts were respectively evaluated for their radical scavenging activity with DPPH (EC50 = 3.39, and 1.06), ABTS (EC50 = 0.690, and 0.55), and peroxide scavenging activity (EC50 = 2.43, and 1.28). GC-MS identified a wide range of compounds that may be responsible for these activities of the results observed. The highest levels of chlorophyll, carotenoids, and lycopene were found in the leaf extract while level of proanthocyanidins was found in the stem peels extract. The peroxidase and catalase activities of stem peel extract were higher than those of the leaf extract. The findings showed that the leaf and stem peel extracts of C. gileadensis exhibited significant antibacterial activity against the test organisms. The minimum inhibitory concentrations for the plant extracts were compared with the standard reference drug Augmentin but the time–kill curves for the C. gileadensis extracts showed that they were less effective than Augmentin. Moreover, the stem peel extract exhibited stronger antibacterial activity than the leaf extract. In conclusion, C. gileadensis can be an important source of natural antioxidants, used as a healthy chewing stick for teeth brushing and oral hygiene purposes.
STUDIES ON PHYTOCONSTITUENTS AND BIOLOGICAL ACTIVITY OF COMMIPHORA BERRYI SYNOPSIS THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY (PHARMACY) IN THE FACULTY OF ENGINEERING AND TECHNOLOGY JADAVPUR UNIVERSITY 2009 BY P.SELVAMANI, M.Pharm DIVISION OF MEDICINAL AND PHARMACEUTICAL CHEMISTRY DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY JADAVPUR UNIVERSITY KOLKATA – 700 032 INDIA STUDIES ON PHYTOCONSTITUENTS AND BIOLOGICAL ACTIVITY OF COMMIPHORA BERRYI This thesis entitled “Studies on Phytoconstituents and Biological Activity of Commiphora berryi” is the narration of the research work which was carried out partly at Department of Pharmaceutical Technology, Jadavpur University, Kolkata and at Department of Pharmaceutical Technology, Anna University Tiruchirappalli, Tiruchirappalli. The importance of natural medicine, basic principles involved and its advantages over the modern medicine is now on focus considering the safety and potency of herbal medicines. The spotlight of this research work was aimed at on the isolation and characterization of phytoconstituents and biological screening of crude extracts of Commiphora berryi. With a brief introduction on natural medicines; a through review on the published literatures about the plant species belonging to the genus Commiphora was presented; since the plant under study was unexplored for its phytoconstituents and biological activity. Evolving out with a focused aim, a compact plan of work, the protocols followed for various experiments such as pharmacognostical and analytical standardization, identification and characterization of isolated phytoconstituents, evaluation of the toxicity studies of the crude extracts and their biological activity studies on analgesic activity, anti-pyretic activity, anti-inflammatory activity, anti-arthritic activity, anti-histaminic activity, anti-malarial activity, anti-oxidant activity, anti-tubercular activity, hepatoprotective activity and urolithiatic activity and the observed results and the conclusions arrived thereof with appropriate bibliographic details were presented. To highlight on the achievements of this research work, the significant findings of this study was summarized as follows. Commiphora berryi (Burseraceae), an unexplored plant was selected for this research work; since the related species i.e., Commiphora mukul, Commiphora molmol and Commiphora wightti were endowed with potent therapeutic potential against diverse ailments and found as a natural repository of spectrum of bioactive compounds. The bark and leaves of this plant was collected after authentication of this plant, dried under shade and powdered. The shade dried material was extracted exhaustively in a soxhlet apparatus with solvents and concentrated under vacuum. The collected herbal raw material and the concentrated crude extracts were then standardized various organoleptic, pharmacognostical (morphological and microscopical) and analytical tests (physicochemical and phytochemical tests etc). The crude ethanol extract of Commiphora berryi (EECB) and petroleum ether extract of Commiphora berryi (PECB) was used for further phytochemical and pharmacological studies. Thin layer chromatographic (TLC) finger printing of the crude extracts were performed to optimize and identify the best solvent that could be utilized for isolation of compounds from the crude extracts based on their Rf values and the degree of separation of phytoconstituents. Column chromatography of the ethyl acetate extract was subjected to chromatography over a silica gel column and eluted successively with petroleum-ether, petroleum ether-chloroform mixture, and chloroform-methanol mixture in the order of increasing polarity. Fractions giving similar spots on TLC were combined and evaporated to dryness under reduced pressure. Monitoring by TLC, the fraction were grouped together. Two major fractions i.e., pet ether-chloroform (3:7) and chloroform-methanol (9.5:5) was taken together and further purified by rechromatography over a column of silica gel (60-120, 30 g) afforded to get pure compound 1 (90 mg) respectively. Compound 1 was recrystalized from chloroform. The structure of the isolated compound was then characterized through Mass, FT-IR, 1H NMR, 13C NMR and DEPT analysis confirmed the compound as Daucosterol whch is a glucopyranoside of β-sitosterol. HPTLC fingerprinting and HPLC analysis of the crude extracts was performed as per the method reported by Agarwal and Mesrob respectively. By comparison with the Rf/Rt values of crude extracts obtained with reference to the Rf/Rt values of authentic compounds; the identity and the amount of E- and Z- isomers of guggulsterones in the crude extracts was confirmed. The crude extracts of bark of Commiphora berryi and the volatile oil collected from the leaves of Commiphora berryi were analyzed through GC-MS. Twenty-two compounds from the petroleum ether extract and eight compounds from the ethanol extract and twenty three compounds from the volatile oil of Commiphora berryi was identified from the GC-MS spectrum by comparison of Rt, molecular weight etc from the NIST database. The crude extracts were subjected to toxicity studies as per the OECD guidelines and the toxicity was determined. Only a minor variation was observed in the various biochemical parameters evaluated; no mortality and gross pathological changes were found in isolated organs in the crude extract treated animals as evidenced through histopathological studies. Hence, the crude extracts were found to be nontoxic upto a dose of 5000 mg/kg and classified as Class I substance as per the Globally Harmonized System was concluded from the toxicity studies performed as per the OECD guidelines in female albino mice. The crude extracts were found to possess significant analgesic activity in mice when evaluated at a dose of 100 and 200 mg/kg as the reaction time is significantly increased in the tail flick model and significantly raised the pain threshold and the analgesic activity at 120 min and 180 min were found to be 35.09% and 31.50% for PECB; and 53.65% and 47.72% for EECB respectively; and at a dose of 200 mg/kg at 120 min and 180 min showed 97.56% and 141.46% for PECB; and 106.1% and 115.90% for EECB respectively. The crude extracts were found to possess significant antipyretic activity in mice, as the rectal temperature is significantly decreased in the yeast induced pyrexia model when evaluated at a dose of 100 mg/kg p.o, EECB exhibited significant antipyretic activity at 240 and 120 min respectively; and at a dose of 200 mg/kg PECB exhibited significant antipyretic activity at 120 and 240 min; EECB at 240 min (P<0.0001). The crude extracts were found to possess significant anti-inflammatory activity in rats when evaluated at a dose of 100 and 200 mg/kg as the paw volume is significantly decreased in the carrageenan, formalin and cotton pellet granuloma model. In carrageenan induced paw odema model the percentage inhibition of EECB at dose of 100 and 300 mg/kg showed a maximum inhibitory response of 51.81 and 73.44% respectively. Similarly, the petroleum ether of CB at a dose of 100 and 300 mg/kg has shown 65.18 and 73.44% respectively. The activity elicited by PECB at 300 mg/kg dose is comparable to the standard drug indomethacin at a dose of 80 mg/kg which produces 74.19% inhibition. In the formaldehyde induced paw odema method; the percentage inhibition of inflammation obtained upon treatment with EECB and PECB at doses of 100 and 300 mg/kg/i.p in rats was found to be 54.34%, 57.97% and 70.28%, 71.39% respectively. The results were comparable to the anti-inflammatory activity (72.46%) elicited by the standard drug indomethacin at the dose of 80 mg/kg. Anti-arthritic activity of the crude extracts of Commiphora berryi was evaluated in complete Freund’s adjuvant induced arthritic model in rats. The extracts were found to possess significant anti-arthritic activity at a dose of 200 and 400 mg/kg as the paw volume is significantly decreased, increase in hyperalgesia, decrease in arthritic index, reversal of decrease in body weight, radiographic analysis and histopathological scoring of bone sections. Administration of the crude extracts of Commiphora berryi (Arn) Engl from day 1 following the induction of arthritis until the end of the experiment developed markedly lower levels of arthritis at significantly lower incidences in a dose-dependent manner The EECB and PECB were evaluated for its anti-histamanic activity in the isolated guinea pig ileum. At a dose of 100 µg/ml; the extracts produced inhibition of histamine induced contraction in guinea pig ileum confirming its H1 receptor antagonistic effect. The extracts produced competitive type antagonism as the antagonistic effect was completely reversed by increasing the concentration of the agonist and the maximal response was achieved with increased concentrations of the agonist. The extracts were found to possess moderate anti-malarial activity when evaluated by 96 well microplate assay against Plasmodium falciparum 3D7 strains. The MIC of EECB and PECB was found to be 25 µg/ml and 100 µg/ml respectively. The extracts were found to possess moderate anti-tubercular activity when evaluated by REMA assay against Mycobacterium tuberculosis H37Rv strains. The sensitivity of the REMA plate for EECB and PECB was 100% at a concentration >100 µg/ml and the specificity was 98.3 and 99.2%, respectively. The extracts were found to possess moderate anti-viral activity when evaluated against the following cell lines. Vero cells: parainfluenza-3 virus, reovirus-1, Sindbis virus, Coxsackie B4 virus and Punta Toro virus; HeLa cells: (cervical carcinoma): vesicular stomatitis virus, Coxsackie B4 virus and respiratory syncytial virus; HEL cells: (human embryonic lung): herpes simplex virus-1 (KOS), herpes simplex virus-2 (G), herpes simplex virus-1 (TK-KOS ACVr), vaccinia virus and vesicular stomatitis virus; Feck cells: Crandell-Recs feline kidney cells, FIPV-antifelline corona virus and felline herpes virus. Reversal of the elevation of AST, ALT, ACP and ALP in serum and thiobarbituric acid reactive substances in CCl4 intoxicated rats by treatment with EECB and PECB at a dose of 100 and 200 mg/kg reduced these values confirmed the hepatoprotective activity. The activity of the antioxidant enzymes i.e., superoxide dismutase, glutathione peroxidase, catalase and bilirubin levels were decreased significantly. Histopathological evaluation further confirms the hepatoprotective activity of the crude extracts. Increase in the volume of urinary excretion, excretion of smaller crystals along with the reduction in the stone forming constituents such as calcium, phosphate, oxalate, urea and creatinine in urine and renal tissue brought about by treatment with PECB and EECB in calculosis induced by glycolic acid administration in rats indicates the potential anti-urolithiatic activity. To conclude about the significant achievements of the research findings were summarized and presented. The certified documents and copies of published articles with other relevant information were provided in the appendix which is added on at the end of this thesis.
Commiphora gileadensis, locally known as becham, is a plant used in traditional Arabian medicine for treating headache, constipation, stomach, joint pain, and inflammatory disorders. Several studies have reported its antibacterial properties; however, no study has demonstrated its antiviral activity. This study aimed to evaluate the antiviral activity of C. gileadensis as well as to isolate its active compound and investigate its mode of action. This activity was evaluated using 4 viruses, herpes simplex virus type 2 (HSV-2), respiratory syncytial virus type B (RSV-B), coxsackie virus B type 3, and adenovirus type 5 by performing the plaque reduction assay and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for enveloped and nonenveloped viruses, respectively. The methanol extract of C. gileadensis leaves only showed antiviral activity against enveloped viruses with a selectivity index of 11.19 and 10.25 for HSV-2 and RSV-B, respectively. The study of the mechanism underlying antiviral activity demonstrated a virucidal effect by direct contact with these target viruses. The active compound, isolated using bio-guided assays involving TLC, was identified as guggulsterone by HPLC-diode array detection coupled with electrospray ionization mass spectrometry. Guggulsterone is an antagonist of the bile acid receptor and a modulator of cholesterol metabolism; however, its antimicrobial properties have been reported for the first time in this study.
Objective: To study the anti-inflammatory and hepatoprotective properties of an ethanolic extract of Parsley 'Petroselinum crispum' leaves. Materials and methods: An ethanolic extract of Parsley was subjected for evaluation of anti-inflammatory and anti-hepatotoxic activities against inflammation induced by carrageenan and cotton pellet granuloma and hepatic damage induced by carbon tetrachloride, respectively in rats. Apart from enzymes, non-protein sulfhydryl (NP-SH) groups were also estimated in liver. Histopathological test on liver was carried out and phenobarbitone-induced sleeping time in mice was also measured in different groups. Results: The phytochemical screening of the extract revealed the presence of flavonoids, tannins, sterols and or triterpenes. The extract exhibited significant protection against carrageenan-induced inflammation, cotton pellet-induced granuloma and CCl 4-induced hepatic damage. Conclusion: Petroselinum crispum exhibited significant anti-inflammatory and anti-hepatotoxic activities which merits further detailed investigations.
The methanol fraction of the extract of Pluchea indica roots exhibited significant hepatoprotective activity against experimentally induced hepatotoxicity by carbon tetrachloride in rats and mice. The extract caused significant reduction of the elevated serum enzyme levels (AST, ALT, LDH and serum alkaline phosphatase) and serum bilirubin content in acute liver injury. A significant increase of reduced serum total protein, albumin and albumin/globulin ratio was also observed on extract treatment. The extract significantly reduced the prolonged pentobarbitone-induced sleeping time and also caused a significant reduction of plasma prothrombin time in comparison with CCl4-treated animals. The extract caused significant reduction of the increased bromosulphalein retention by CCl4-treatment. These findings are suggestive of a potent hepatoprotective effect of the extract under investigation.
The hepatoprotective effect of various fractions (n-hexane, CHCl3, EtOAc, n-BuOH, and H2O) of Ban-zhi-lian derived from Scutellaria rivularis Benth. was studied against carbon tetrachloride (CCl4), d-galactosamine (d-GalN) and acetaminophen (APAP)-induced acute hepatotoxicity in rats. Liver damage was assessed by quantifying serum activities of glutamate oxaloacetate transaminase (sGOT) and glutamate pyruvate transaminase (sGPT), as well as by histopathological examination. The results indicated that the CHCl3 fraction and EtOAc fractions exhibited the greatest hepatoprotective effects on CCl4-induced liver injuries, the CHCl3 fraction and n-hexane fraction are most potent against d-GalN-induced intoxication, and the CHCl3 fraction represented the most liver-protective effect on APAP-induced hepatotoxicity. The pathological changes of hepatic lesions caused by these three hepatotoxicants were improved by treatment with the fractions mentioned above, which were compared to Glycyrrhizin (GLZ) and Silymarin as standard reference medicines.
Hepatoprotective activity of the n-heptane extract of Cassia fistula leaves was investigated in rats by inducing hepatotoxicity with carbon tetrachloride:liquid paraffin (1:1). The extract has been shown to possess significant protective effect by lowering the serum levels of transminases (SGOT and SGPT), bilirubin and alkaline phosphatase (ALP). The extract of C. fistula at a dose of 400 mg/kg showed significant hepatoprotective activity which was comparable to that of a standard hepatoprotective agent.
Aspartate aminotransferase (EC activity and the distribution of its isoenzymes in human liver were examined. Rabbit antiserum against porcin soluble (i.e., non-mitochondrial) enzyme cross-reacted with the soluble enzyme of human origin and was used in an immunoprecipitation assay to quantitate the soluble and mitochondrial isoenzymes. These were separated by rapid, semiquantitative electrophoresis on cellulose acetate and by three other quantitative techniques: isoelectric focusing and anion-and cation-exchange chromatography. The mitochrondrial enzyme averaged 81% of the total activity in normal adult human liver (n = 4). Its contribution was dramatically reduced in single specimens of human fetal liver (56% of total activity) and hepatoblastoma tissue (38%). Total enzyme activities (mumol min-1 per gram of tissue) were: adult, 150; fetal, 38; tumor, 6. Total enzyme concentrations (micromoles of enzyme per kilogram of tissue) found were: adult, 10.8; fetal, 2.7; tumor, 0.4. The concentrations and isoenzyme distribution in human liver are compared to those in various animal model systems. Other methods for quantitative estimation of the isoenzymes and their adaptability for use in estimating concentrations in serum are reviewed.
CCI4 has long served as a model compound for study of hepatotoxicity. While its simple chemical structure held the allure of a simple mechanism of action, decades of study have disclosed a complex series of responses. Significant early damage following CCI4 administration includes: (1) A number of alterations affecting Ca2+ homeostasis, which conspire to redistribute cellular Ca2+ from endoplasmic reticulum and mitochondria to cytosol, and (2) hypomethylation of ribosomal RNA, which disrupts protein synthesis. The genesis of the injury in vivo appears to encompass early 'metabolism-dependent' effects (which appear to be largely independent of CCI4 concentration at the levels studied) and later 'metabolism-independent' effects, which parallel CCI4 concentration. The inability of injured hepatocytes to respond anabolically to early damage may be a critical feature in CCI4 hepatotoxicity.
The petroleum ether extract of the oleo-gum resin of Commiphora molmol, at a dose of 500 mg/kg body weight, produced significant inhibition of carrageenan induced inflammation and cotton pellet granuloma. The extract also showed significant antipyretic activity in mice. Further studies on the fractionation of phytoconstituents and their mechanism of action are in progress.