Protective effects of Aristolochia longa and Aquilaria malaccensis against lead-induced oxidative stress in rat cerebrum


Samir Derouiche*, Khaoula Zeghib, Safa Gherbi, Yahia Khelef

Department of Cellular and Molecular Biology, Faculty of Natural Science and Life, University of Echahid Hamma Lakhdar-Eloued, El-oued 39000, El-oued, Algeria

*Corresponding Author E-mail:



The present study was conducted to investigate the treatment with Aristolochia longa (A. longa) and Aquilaria malaccensis (A. malaccensis) (widely used in Algerian traditional medicine) in reversing lead-induced oxidative stress in the cerebrum of rat. For this purpose, 25 adult female Wistar albino rats, equally divided into control and four treated groups,received eitherlead (Pb), Pb+A. longa(Ar), Pb+A. malaccensis(Aq), or Pb+Ar+Aq. lead (100 mg/kg b.w)as Lead(II) acetate added in their drinking water for 75 days.A. longa(rhizome powder at a dose 1% of diet) and  A. malaccensis (heartwood powder at a dose 1% of diet) were added to the feed during the last 15 days of lead exposedin the animals.The results of the phytochemical screening revealed that A. longaand A. malaccensis aqueous extract contained various bioactive compounds, including polyphenols, saponins, terpenoids, glycosides and flavonoids. Total phenolic content in A. longa and A malaccensis aqueous extract was found a high level. The results showed also that Pb treatment increased significantly the cerebrum level of Malondialdehyde (MDA) and Catalase (CAT) activity, whereas the Glutathion S transferase (GST)activity and the cerebrum levels of reduced glutathione (GSH) were decreased compared to control rats. Our results showed that treatment with A. malaccensis and A. longa partially reversed this change. Results demonstrated beneficial effects of A. longa and A. malaccensis treatment in Pb-induced oxidative stress in cerebrum and suggest that A. longa could therefore be considered a promising source of novel treatments for cerebrum alterations.


KEYWORDS: A. longa, A. malaccensis, Cerebrum, Lead acetate, Oxidative stress.











Lead is a ubiquitous environmental and industrial pollutant that has been detected in every facet of environmental and biological systems. Lead can be found in water pipes, insecticides, lining of equipment where corrosion resistance and pliability are required, in petroleum refining [1]. Lead is known to induce a broad range of physiological, biochemical, and behavioral dysfunctions in laboratory animals and humans, including central and peripheral nervous systems, haemopoietic system, cardiovascular system, hepatic, and kidney [2]. encephalopathy (a progressive degeneration of certain parts of the cerebrum ) is a direct consequence of lead exposure and the major symptoms include dullness, irritability, poor attention span, headache, muscular tremor, loss of memory and hallucinations [3]. At higher levels, lead can cause permanent cerebrum  damage and even death. There is evidence suggesting that low level lead exposure significantly affects IQs along with behavior, concentration ability and attentiveness of the child [4]. One of the major mechanisms behind heavy metal toxicity has been attributed to oxidative stress [5]. Toxic metals increase production of free radicals and decrease availability of antioxidant reserves to respond to the resultant damage stress [6]. A growing amount of data provide evidence that metals are capable of interacting with nuclear proteins and DNA causing oxidative deterioration of biological macromolecules, eventually leading to many chronic diseases, such as atherosclerosis, cancer, diabetes [7.8]. Thus, there has been an increased interest in the therapeutic potential of plant products or medicinal plants having antioxidant properties in reducing free radical-induced tissue injury , such as phenolic compounds, nitrogen compounds, vitamins, terpenoids, and some other endogenous metabolites, which are rich in antioxidant activity [9]. Aristolochia longa L. (Aristolochiaceae) locally called “Beroustoum” is a species commonly used in Algerian traditional medicine. It has multiple applications and virtues; it is recommended for ovarian failure, healing, diuretic, analgesic, anti-inflammatory, anti-mitotic [10]. Aquilaria Malaccensis (Agarwood) is a species widely distributed south-east Asia and considered to have a broad spectrum of therapeutic effects. These include antioxidant activities, analgesic, antipyretic, anti-inflammatory, antihyperglycemic , and antimicrobial [11] The aim of present study was designed to investigate the effect of Aristolochia longa and  Aquilaria Malaccensis on cerebrum  toxicity induced by lead and to evaluate phytochemical composition and polyphenols contents and some antioxidant parameters.



2.1. Collection and Preparation of the aqueous extract

A. longa roots and A. malaccensis  heartwood  were collected in herbalists shops from a local market of El-oued. The vegetal material was washed with water, and then dried at room temperature for 48 to 92 h. grounded into powder and stored at room temperature until use. The aqueous extract was prepared by adding 500 ml of distilled water to 50 g dry powder of A. longa or A. malaccensis  . After 24 h of maceration at room temperature, the mixture was centrifuged, filtered and then concentrated in a rotary vacuum evaporator [12].





2.2. Phytochemical Screening.

The screening of extracts for the presence of phytochemicals like alkaloids, saponins, tannins, flavonoids, terpenoids and glycosides was performed according to the method given by Mamta and Parminder (2013) [13].


2.3. Determination of Total Phenolic Content

Total phenolic content was measured using the Folin– Ciocalteu’s reagent as described by Mamta and Parminder (2013) [13].


2.4. Animals and Handling.

Twenty five  adult females albino rats, weighing 224–230 g, were brought from the animal house of Pasteur institute, Algeria. They were placed in five groups of 5 rats in each and kept in animal’s house of Molecular and cellular biology Department, University of El oued, Algeria. Standard rat food  and tap water were available ad libitum for the duration of the experiments unless otherwise noted [14]. Animals were acclimated for two weeks under the same laboratory conditions of photoperiod (12h light/12 h dark) with a relative humidity 62.3 % and room temperature of 25 ± 2 C°. The experimental procedures were carried out according to the National Institute of Health Guide-lines for Animal Care and approved by the Ethics Committee (n°=32BCM/SNV/2017) of our Institution.


2.5. Experimental design

The experiment was conducted over a period of 10 weeks. After a period of adaptation, the animals, at the age of 08 weeks ,were divided into five experimental groups of 5 animals each: the control group was not treated with Pb and the remaining four experimental groups received either lead (Pb), Pb + Aristolochia longa, Pb+ Aquilaria malaccensis , or Pb+ AL+AM.  lead (100 mg/kg b.w) as Lead(II) acetate added in their drinking water for 75 days. Aristolochia longa (rhizome powder (Ar) at a dose 1% of diet ) and Aquilaria malaccensis  (heartwood powder (Aq) at a dose 1% of diet) were added to the feed during the last 15 days of lead exposed in the animals. evaluate the food intake, drinking water and body weight were  monitored during the whole experiment.


2.6. Preparation of tissue samples

At the end of 2 weeks of Aristolochia longa and Aquilaria malaccensis  treatment, rats were fasted for 16 hrs, anaesthetized with chloroform by inhalation, rats  were  decapitated  and  cerebrum   was rapidly excised, weighed and   stored   at- 20° C for   oxidative   stress   parameters analysis.





2.7. Antioxidants measurement.

2.8. Preparation of homogenates 

About 0.5 g of cerebrum  was homogenized in 2 ml of buffer solution of phosphate buffer saline 1:2(w/v; 1g tissue 2ml TBS, pH=74). Homogenates were centrifuged at 10000xg for 15 min at 4°C, and the obtained supernatant was used for the determination of antioxidant activity.


2.9. Determination of Malondialdehyde (MDA) level

tissue homogenates were prepared at 10% (w/v) in 0.1 mol/L Tris-HCl buffer, pH 7.4, and MDA steady-state level was determined. MDA was measured according to the method described by Sastre et al. (2000) [15]. Thiobarbituric acid 0.67% (w/v) was added to a liquots of the homogenate previously precipitated with 10% trichloroacetic acid (w/v). Then the mixture was centrifuged, and the supernatant was heated (100°C) for 15 min in a boiling water bath. After cooling, n-butanol was added to neutralize the mixture, and the absorbance was measured at 532 nm. The results were expressed as nmol of MDA/g tissue.


2.10. Determination of reduced glutathione (GSH) level

GSH concentration was performed with the method described by Ellman [16]. based on the development of a yellow color when DTNB is added to compounds containing sulfhydryl groups. In brief, 0.8 mL of tissue homogenate was added to 0.2 mL of 0.25% sulphosalylic acid and tubes were centrifuged at 2500 g for 15 min. Supernatant (0.5 mL) was mixed with 0.025 mL of 0.01 M DTNB and 1 mL TBS (pH 7.4). Finally, absorbance at 412 nm was recorded. Total GSH content was expressed as nmol GSH/mg protein.


2.11. Determination Glutathione-S-transferase (GST) activity

Glutathione-S-transferase (GST) activity of tissues was measured spectrophotometrically by the  method of Habig et al. [17]. using CDNB as electrophilic substrate that binds to GSH with the participation of the enzyme and forms a colored GSH-substrate complex, detected at 340 nm. The activity of GST was expressed in terms of μmol CDNBGSH conjugate formed/min/mg protein.


2.12. Determination of Catalase (CAT) activity

Catalase activity (CAT) measured using the method of Sinha [18]. It is based on the fact that dichromate in acetic acid is reduced to chromic acetate when heated in the presence of H2O2, with the formation of perchromic acid as an unstable intermediate. The chromic acetate thus produced is measured calorimetrically at 570~610 nm. Since dichromate has no absorbance in this region, the presence of the compound in the assay mixture does not interfere at all with the colorimetric determination of chromic acetate. The catalase preparation is allowed to split H2O2 for different periods of time. The reaction is stopped at a particular time by the addition of dichromate/acetic acid mixture and the remaining H2O2 is determined by measuring chromic acetate calorimetrically after heating the reaction mixture.


2.13. Statistical Analysis

The reported data are the means of measurements and their standard error of mean (SEM) values. For statistical evaluation, the Student’s t-test and P < 0.05 was considered the limit for the statistical significance.



3.1. Phytochemical Screening and total phenol content.

Phytochemical analysis revealed the presence of alkaloids, glycosides, tannins and phenolic compounds, flavonoids, Terpenoids and saponins in the extract (table 1). Quantitative analysis of the phenolic components of A. Malaccensis  and A. longa results showed that they contains high level of totale phenol as showed  in table 2.


Table 1

Phytochemical composition of water extracts of rhizome Aristolochia longa and heartwood Aquilaria malaccensis.  


A.       A. Longa

A.       A. Malaccensis






















+ = Present; - = Absent


Table 2

Total phenolic content of water extracts of rhizome A. longa and heartwood A. malaccensis.


B.      Total Phenolic Conent

C.      mg(GAE)/g

Aquilaria  nalaccensis

11.767 ± 0.05

Aristolochia longa

14.223 ± 0.207


3.2. MDA Concentrations

There was a significant (p<0.05) increase in MDA concentrations in cerebrum  tissues after Pb treatment for 75 consecutive days (0.38±0.04 μmol/mg protein) compared to the control group (0.25±0.04 μmol/mg protein; Fig. 1). The treatment of Pb -exposed rats with A. malaccensis  or A. longa decrease significantly the MDA cerebrum  level (0.31±0.08μmol/mg protein and 0.31 ± 0.07 μmol /mg protein) respectively as compared to the  Pb exposed group. Interestingly, our results showed that co-treatment with A. malaccensis  and A. longa partially reversed this change (0.312 ±0.15μmol/mg protein). In fact, MDA concentrations in the Pb +Aq, Pb + Ar and Pb+Aq +Ar groups  were significantly higher than in the control group (p<0.01).




Figure. 1 Level of MDA in cerebrum  tissues of control (C) and experimental groups. Means± SE from 5 animals in each group. Significance from C: *p<0.05, **p<0.01. Significance from Pb: a p<0.05, c p<0.001.


3.3. GSH Concentrations

The GSH level was significantly decreased (p<0.01) in Pb -exposed rats (0.087±0.005 nmol/mg protein) as compared to control rats (0.105±0.010 nmol/mg protein; Fig. 2). The treatment of Pb -exposed rats with Aq or Aq+Ar had no effect on the Pb -induced decrease in the GSH level, whereas With the A. longa treatment alone we noticed a complete prevention from the Pb -induced decrease in GSH cerebrum  level(0.110±0.007 nmol/mg protein) .



Figure. 2 Level of GSH in cerebrum  tissues of control (C) and experimental groups. Means± SE from 5 animals in each group. Significance from C: *p<0.05, **p<0.01, ***p<0.001. Significance from Pb: b p<0.01


3.4. GST Activity

The data presented in Fig. 3 showed that the exposure to Pb  led to a significant decrease (p<0.001) in GST activity (2.20±0.09 nmol/min/mg protein) compared to the control (2.98±0.43 nmol/min/mg protein). Aq treatment alone or in combination with Ar  had no significant effect on Pb -induced increase in the GST activity, whereas Ar treatment alone entirely reversed this change (3.03±0.68 nmol/min/mg protein) .


Figure. 3 Activity of GST in cerebrum  tissues of control (C) and experimental groups. Means±SE from 5 animals in each group. Significance from C: *p<0.05, ***p<0.001. Significance from Pb: b p<0.01.



3.5. CAT Activity

As shown in Fig. 4, exposure to Pb  induced a significant (p<0.01) increase in CAT activity (7.382±0.278 U/mg protein) compared with control rats (5.45±0.212 U/mg protein). When rats were concomitantly exposed to Aq  or Ar, activity of CAT (5.81±0.249 U/mg protein and 5.702± 0.615 U/mg protein ) was significantly higher than in Pb -exposed rats (p<0.01 and p<0.05  ) respectvely. Aq combined with Ar  treatment had no significant effect on the Pb -induced increase in the MDA concentrations.


Figure. 4 Activity of CAT in cerebrum  tissues of control (C) and experimental groups. Means ± SE from 5 animals in each group. Significance from C: *p<0.05, ***p<0.001. Significance from Pb: a p<0.01, c p<0.01


Through this study, we investigated the potential benefit of treatment with rhizome powder of A. longa and heartwood powder of A. malaccensis in reversing Pb-induced cerebrum  oxidative stress in rats orally exposed to Pb. Our results of the phytochemical screening revealed that A. longa and A. malaccensis aqueous extract contained various bioactive compounds, including terpenoids and flavonoids. The highest reducing power and amount of total phenolic compounds was shown by aqueous extract of A. malaccensis  and A. longa. Recently, bioflavonoids and polyphenols of plant origin have been used extensively for free radical scavenging and to inhibit lipid peroxidation. These antioxidant compounds could have played a major role in scavenging the reactive oxygen species induced by lead acetate [19]. From the results of our study it is seen that administration of lead to rats caused a significant increase in the level of lipid peroxidation as indicated by the significant increase in MDA. Our results also corroborate well with that of Adonaylo and Oteiza (1999) [20] and Kansa et al (2011) [21]. who demonstrated that lead increases the rate of lipid peroxidation in cerebrum. Oxidative stress is caused by a relative overload of oxidants, reactive oxygen species [22]. According, the Pb may cause oxidative stress by two separate, although related, pathways: the generation of ROS, including hydroperoxides, singlet oxygen, and hydrogen peroxide, and the depletion of antioxidant reserves [23]. The central nervous system is vulnerable to reactive oxygen species (ROS)-mediated injury because of a high rate of oxidative metabolic activity, high concentration of readily oxidizable substances (membrane polyunsaturated fatty acids), and endogenous generation of ROS by specific neurochemical reactions and high ratio of membrane surface area to cytoplasmic volume[24]. Moreover, under normal conditions, the cerebrum  is susceptible to oxidative damage due to its high oxygen consumption rate (in humans, the cerebrum  uses ~20% of the circulating glucose, 20% of blood’s oxygen and occupies 2% of the body weight), to high levels of polyunsaturated fatty acids (PUFA), and to a progressive accumulation of iron levels with aging [25] and paradoxically its deficient oxidant defense mechanisms and its diminished cellular turn over [26]. Neurotoxicity associated with Pb exposure may be the result of a series of small perturbations in brain metabolism, and, in particular, of oxidative stress. Pb stimulated lipid peroxidation resulted in the formation of aldehydic by-products, which in turn caused a decrease in reduced glutathione content. In addition, the higher level of malondialdehyde in the brain of Pb-exposed rats indicates increased lipoperoxidation and potential neuronal membrane damage. In fact, the increased lipid peroxidation detected in the brain of lead treated rats in the present study confirms previous results [27]. The enhanced lipid peroxidation might result from the reduction in the cerebrum activities of GST and GSH level observed in these animals. In agreement with previous studies, the level of GSH in cerebrum  was significantly decreased upon oral Pb administration compared to the control group. Glutathione (GSH) participate in the cellular defense system against oxidative stress by scavenge free radicals and reactive oxygen intermediates [28]. This decrease in GSH levels may be due to its consumption in the scavenging free radicals generated by lead, also Pb binds exclusively to the thiol groups which decrease the GSH levels thereby interfering with the antioxidant activity [29]. The results of our experiments showed that, in animals exposed to Pb, the CAT activity was significantly increased. Similar results have been reported [30]. The pro-oxidant role of lead is not known but the inhibition of delta amino levulinic acid dehydratase causes accumulation of delta amino levulinic acid which on auto-oxidation results in the formation of superoxide and hydrogen peroxide [31]. Since oxidative stress is the first response to the environmental pollutants, cerebrum  cells may stimulate antioxidant and detoxification responses to counter heavy metal damages. The involvement of antioxidative enzymes such as GST play a considerable mission in protecting cells from oxidative stress [32] So, assessment of activities of this enzyme may supply important informations about oxidative stress that cells exposed. We determined that lead used in this study were decreased enzyme activity.  Similar results have been also reported by Sarkar et al. (2014) [33]. The treatment of Pb-exposed animals with A. longa or A. malaccensis  alone or Their combination partially reversed Pb-induced increase in MDA level and CAT activity and Pb-induced decrease in GSH level and GST activity. Secondary metabolites produced by plants possess several interesting biological activities, and are a source of pharmacologically active [34]. Since biological activities of medicinal plants are closely related to their chemical compounds [35]. Phytochemical screening of A. longa and A. malaccensis aqueous extract revealed the presence of polyphenols, flavonoids, alkaloids, carbohydrates, and saponins. The available data indicate that A. longa and A. malaccensis  are one of the most important source of total phenol content.  The antioxidant capacity of A. longa and A. malaccensis  extracts is mainly related to their higher level of phenolic compounds (14.22 and 11.76 mg GAE/g) respectively. These latter are well known for their ability of scavenging free radicals such as superoxide radical (O2.), hydroxyl radical (OH.) and others ROS. These   molecules   are   the   primal   source   of antioxidant  ability  of  A. longa and A. malaccensis  reducing the oxidative stress   by  scavenging  free  radicals as hydroxyl radical (OH .) which is the major cause of lipid peroxidation [36. 37]. Indeed Natural phenolic  compounds  play  an  important  role  in  cancer   prevention  and  treatment.  Various  bioactivities  of  phenolic  compounds   are   responsible   for   their   chemopreventive    properties   (e.g.,   antioxidant,   or antimutagenic and anti-inflammatory effects) regulating carcinogen metabolism, inhibiting DNA binding and cell adhesion, migration, proliferation  or  differentiation,  and  blocking  signalling  pathways  [38]. Flavonoids  possess  strong  cytotoxic  and apoptogenic  activities  against  several  cancer  lead induced. This fact is confirmed by the significant lowering MDA and CAT level and increased GSH and GST antioxidant levels in cerebrum. The current study was different than that reported by Benzakour et al. (2011) [39] who reported that  administration  of  the  aqueous  extract  of  A.  longa at  saturation limit dose (2.5 g/kg) produced severe and irreversible renal toxic effects in mice induced by a high immunostimulation activity.



The current study shows an increase in the antioxidant activity as implicated in the cerebrum tissue homogenate of rat treated with the rhizome powder of A. longa or heartwood powder of A. malaccensis, in regards to this it is clearly shown that A. longa could be cerebral protective  and thereby serve as a means of preventing some of the major degenerative diseases



We declare that we have no conflict of interest.



We thank members of Algiers Pasteur Institute for providing the rats.



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Received on 18.11.2018                Modified on 16.12.2018

Accepted on 31.12.2018            © A&V Publications All right reserved

Asian J. Res. Pharm. Sci. 2019; 9(1):57-63.

DOI: 10.5958/2231-5659.2019.00010.9