• Users Online: 168
  • Print this page
  • Email this page


 
 
Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 30  |  Issue : 4  |  Page : 151-156

Olea europaea subsp. Cuspidata and Juniperus procera hydroalcoholic leaves' extracts modulate stress hormones in stress-induced cystitis in rats


1 Department of Surgery, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
2 Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
3 Department of Anatomy and Embryology, Faculty of Medicine, Zagazig University, Egypt
4 Departments of Clinical Pharmacy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
5 Department of Medical Graduates (Interns), Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
6 Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
7 Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

Date of Submission23-Oct-2018
Date of Decision08-May-2019
Date of Acceptance16-May-2019
Date of Web Publication29-Jul-2019

Correspondence Address:
Naiyer Shahzad
Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah
Saudi Arabia
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/UROS.UROS_130_18

Get Permissions

  Abstract 


Objective: To study the effect of Saudi medicinal plant in stress-induced cystitis in experimental rats. Materials and Methods: Seventy-two female Sprague Dawley rats (200–250 g) were divided into eight groups of 9 rats each. Group 1 and 2 are controls assigned nonstressed and stressed, respectively. Other six groups received different treatments for 2 weeks. After the 14 days of treatment, each group was exposed to water-immersion restraint stress (WIRS) for 30 min. Blood samples were collected to measure the corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) levels. The rats were sacrificed, and their urinary bladders were isolated immediately for a histological and immunohistochemical examination. Results: Rats exposed to WIRS had lesions in the urinary bladder, with a significant increase in plasma CRH and ACTH levels in comparison to the nonstressed controls. Bladder cut sections in stressed rats showed no gross structural abnormality in smooth muscle and connective tissue ratio. There were noticeable variations in mast cell (MC) infiltration and activity with a loss of more than 20% of cellular staining and a significant increase in the number of red blood cell-filled blood vessels. Our findings showed that supplementation of Olea europaea leaf extract (OEE) or Juniperus procera leaf extract (JPE) reduced the MC infiltration and significantly reduced stress hormones compared to the stressed controls. Conclusions: The present study demonstrated that OEE/JPE alone and their combination have a potential protective effect against stress-induced cystitis in rats. The underlying mechanism of the present study also resulted in a decrease in CRH and ACTH stress hormones.

Keywords: Interstitial cystitis, Juniperus procera, Olea europaea, plant leaves, rats


How to cite this article:
Nassir AM, Aziz Ibrahim IA, Afify MA, ElSawy NA, Imam MT, Shaheen MH, Basyuni MA, Bader A, Azhar RA, Shahzad N. Olea europaea subsp. Cuspidata and Juniperus procera hydroalcoholic leaves' extracts modulate stress hormones in stress-induced cystitis in rats. Urol Sci 2019;30:151-6

How to cite this URL:
Nassir AM, Aziz Ibrahim IA, Afify MA, ElSawy NA, Imam MT, Shaheen MH, Basyuni MA, Bader A, Azhar RA, Shahzad N. Olea europaea subsp. Cuspidata and Juniperus procera hydroalcoholic leaves' extracts modulate stress hormones in stress-induced cystitis in rats. Urol Sci [serial online] 2019 [cited 2019 Aug 23];30:151-6. Available from: http://www.e-urol-sci.com/text.asp?2019/30/4/151/263646




  Introduction Top


Cystitis is an inflammatory bladder disease manifested as pelvic, bladder, and urethral pain. The most common cause of chronic cystitis is interstitial cystitis (IC)/painful bladder syndrome (PBS);[1] in addition, it has significant disruption in voiding effects. IC/PBS affects all age groups of either sex.[1] The International Continence Society describes it as “the complaint of suprapubic pain related to bladder filling, accompanied by other symptoms such as increased day and night-time frequency in the absence of proven urinary infection or other obvious pathology of the lower urinary tract.” The prevalence of IC/PBS is 14-fold higher in females than in males.[2]

To date, the etiology of this disease is not completely understood. Moreover, some studies suggest that individuals with IC/BPS are 4.37 times more likely than controls to have a prior diagnosis of stress or anxiety disorders, and this strong association might identify important clues to the pathogenesis and pathophysiology of IC/BPS.[3] Stress causes a sympathetic effect leading to the initiation of inflammatory processes in IC. Stress has shown to activate bladder mast cells (MCs), apparently through the action of at least some sensory neuropeptides.[4] These outcomes have implications for the pathophysiology and possible treatment of IC.

Stress is known to initiate the hypothalamic–pituitary–adrenal axis [5] and thus can influence defects [5] related to the immune system, especially neuroinflammatory disorders. These impacts are most likely intervened through both psychoneuroimmune and neuroendocrine-resistant associations that add to the aggravation and inflammatory reactions [6] and intensify certain neuroinflammatory conditions, such as headaches, neurogenic pruritus, and IC, all of which have been associated with MC initiation.[6],[7]

Currently, there is a huge and wide interest in using natural medicinal products in the prevention and treatment of many illnesses.[8] Historically, in Saudi traditional medicine, Olea europaea (OE) and Juniperus procera (JP) have been used as a combination for treating inflammatory bladder conditions and prostatic hypertrophy for a long time. The leaves and fruits of OE contain several pharmacological active constituents including polyphenols and flavonoids.[9] The most abundant compound in olive leaf extract (OLE) is oleuropein, followed by hydroxytyrosol. The main polyphenols are luteolin, apigenin, and verbascoside.[10] Other bioactive constituents of OLE include triterpenes, such as oleanolic acid,[11] rutin, and diosmin.[12],[13],[14] Oleuropein is considered to have great potential as an antioxidant and food additive but also as a possible therapeutic option.[8],[9],[10],[11],[12] A wide range of studies on oleuropein have been performed using in vitro assays, animal models of disease, and human volunteers, to explore possible beneficial effects for human health.[15]

JP knew in Arabic (Ar'ar) is used for many medical purposes.[16] It is widely distributed in the southern part of the Arabian peninsula (Saudi Arabia and Yemen), Eastern Africa (including Sudan and Zimbabwe), and to some extent, the Americas.[16],[17] Different parts of the plant (leaves, berries, and bark) are used for the treatment of various diseases such as asthma, sore throat, pneumonia, tuberculosis, bronchitis, hyperglycemia, eczema, and skin rash. It has also used for the treatment of jaundice and in wound healing.[18],[19],[20] In traditional medicine, Juniperus species are used as remedies against the common cold, urinary infections, urticaria, dysentery, hemorrhage, rheumatic arthritis, and to relieve menstrual pain in many parts of the world.[21],[22],[23]

This study aimed to estimate the possible protective effect hydroalcoholic extracts of OE subsp. Cuspidata and JP leaves against stress-induced cystitis in female Sprague Dawley rats and the effect of treatment on the stress hormones, i.e., corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) in rats exposed to water immersion-restraint stress (WIRS).


  Materials and Methods Top


This study is an interventional study using animal models. The rats were divided randomly into eight groups and keep in cages (5 rats/cage) in the animal house of Umm Al-Qura University, Faculty of Medicine.

Animals

Seventy-two adult female Sprague-Dawley rats approximately 4 months of age at study initiation, weighing 200–250 g, were got from the animal house of the faculty of medicine Umm Al-Qura University. The rats were individually housed in high-quality polyethylene cages with stainless steel wire mesh flooring in a controlled environment at 23°C–25°C and 50% humidity with a 12-h artificial light cycle on a 12:12-h dark-light cycle (07.00–19.00 lights on). Food was maintained on a pellet diet and tap water ad libitum during the entire period of the study. At the end of the experimental study, it was sacrificed rats for rapid urinary bladder isolation for histological and immunohistochemical examination.

Plant material collection and extraction

The leaves of OE subsp. Cuspidata and JPwere collected in 2016 at Wadi Thee Ghazal, Taif Region, Saudi Arabia (GPS Coordinates: 21.092098, 40.379891). The voucher specimens were preserved in the Herbarium of Pharmacognosy Lab at Umm Al-Qura University with the number (UQU-Med 2015/1 for OE subsp. Cuspidata and UQU-Med 2015/2 for JP). The extracts were prepared by maceration and stirring of 50 g of each dry and powdered plant material in 1 L of a 50% hydroalcoholic solvent (50% ethanol + 50% distilled water v/v). Then, the extracts were filtered separately and dried using a rotary evaporator. The yield of OEand JPextracts (JPE) was 19.3% and 17.8%, respectively. Furthermore, these extracts were stored in a refrigerator for subsequent experimental use.

Study protocol

A total of 72 healthy Sprague Dawley female rats were divided randomly into 8 groups of 9 rats in each group. Blood samples were collected at day zero of treatment. The treatment was given according to the following treatment plan:

  • Group 1 – Normal control group treated with physiological saline orally 10 ml/kg body weight not subjected to stress
  • Group 2 – Treated with physiologic saline orally 10 ml/kg body weight and subjected to stress


  • Group 3 Administered pentosan polysulfate 30 mg/kg body weight
  • Group 4 – Administered OEextract (OEE) 500 mg/kg body weight
  • Group 5 – Administered OEE 250 mg/kg body weight
  • Group 6 – Administered JPE 500 mg/kg body weight
  • Group 7 – Administered JPE 250 mg/kg body weight
  • Group 8 – Combined extracts of JPE and OEE administered each 250 mg/kg body weight.


All the drugs were administered using oral gavage for 14 days and all the rats were subjected to stress except normal control (Group 1). The rats were deprived of food for 24 h before the experiment. Stress was induced by placing the animals into a plexiglass immobilizer (Harvard Instruments, Cambridge) located on a bench top and restrained for 30 min at room temperature. The experiment was done at the same time of the day to avoid the diurnal rhythm. After exposure to stress, the rats were anaesthetized by injecting both ketamine (100 mg/kg) and xylazine (15 mg/kg). The rats were then sacrificed, and blood samples were collected in different vacutainer from the inferior vena cava. CRH and ACTH values were determined by automated ELISA Kits.

Histological technique

Urinary bladder specimens were taken from the pelvis and were cut into sections (~ 4–5 μm thickness). Proper fixation was done using 10% neutral-buffered formaldehyde. The tissues were then dehydrated, cleared in xylol, and embedded in paraffin wax. Finally, the bladder sections were stained with hematoxylin and eosin stain [12] and the 0.5% acidified stain (pH <2.5) toluidine blue (Sigma, St. Louis). Two individuals independently counted all MCs, each blinded to the experimental conditions. Each cross-sectional specimen was examined for (a) total number and activity of MCs: (1) resting (not degranulated), (2) partially activated (released < 20% of granules), and (3) fully activated (released >20% of granules). A total of 2–4 sections were counted for each bladder specimen, and the mean was calculated using image analyzer (Leica Imaging System, LTD) (b) bladder inflammation was measured according to the following score criteria: (1) mild infiltration with or without mild edema, (2) moderate infiltration with moderate edema, and (3) severe infiltration with severe edema.

Statistical analysis

The data were expressed as the mean ± standard error of mean and were analyzed using the Statistical Package for Social Sciences (SPSS for Windows®, version 23.0, IBM Corporation). Statistical comparisons were performed by a two-way analysis of variance. The results were considered statistically significant if P < 0.05.


  Results Top


Corticotropin-releasing hormone

In Group 2 (stress control), the value of CRH was highly elevated, which indicated severe stress and inflammation. Group 4 (OE 500 mg/kg)-treated rats showed a highly significant (P = 0.004) decrease. Group 5 (OE 250 mg/kg; P = 0.0492), Group 6 (JP 500 mg/mg; P = 0.039), and Group 8 (OE + JP 250 mg/kg each; P = 0.048) exhibited a significant decrease in CRH values. There was a nonsignificant numerical decrease in Group 3 (PPS 30 mg/kg; P = 0.069) and Group 7 (JP 250 mg/kg; P = 0.062). As a consequence of these values, the rats that were exposed to WIRS had IC and a significant increase in the plasma CRH levels in comparison to the nonstressed control [Table 1].
Table 1: Serum corticotropin-releasing hormone levels (pg/ml) and serum adrenocorticotropic hormone levels (pg/ml)

Click here to view


Adrenocorticotropic hormone

In Group 2 (stress control), the ACTH value was highly elevated which indicated severe stress and inflammation. Group 4 (OE mg/kg; P = 0.004) and Group 6 (JP 500 mg/kg; P = 0.003) showed a highly significant decrease in ACTH values. Group 5 (P = 0.042), Group 7 (P = 0.039), and Group 8 (P = 0.048) showed significant decrease in plasma ACTH while Group 3 had no significant changes [Table 1].

Histopathology

Normal control (saline-treated) groups showing normal histology of the urinary bladder muscle layer, urothelium, and lamina propria were subdivided into a superficial dense irregular layer and a deep loose layer containing small blood capillaries (average MC number = 1) [Figure 1]a and [Figure 1]b. Urinary bladder sections in stress model rats showed no gross structural abnormality in smooth muscle and connective tissue ratio but obvious variations in MC filtration, with a MC activation loss of more than 20% cellular staining and a significantly greater number of red blood cell-filled vessels. Multiple detachments, vacuolation, and focal decrease in the urothelium (uroepithelium) cell layers and disrupted lamina propria containing dilated blood vessels and leukocytes infiltration with multiple MCs (average MC number = 9 with Grade 3 inflammation) were observed [Figure 2]a and [Figure 2]b. In Group 3, rats showed minimal detachment of urothelium and minimal infiltration without edema (average MC number = 3 less than Grade 1 inflammation) [Figure 3]a and [Figure 3]b. In Group 4, mild infiltrations in lamina propria, detached mucosa with vacuoles, and mild edema (average MC number = 4 with Grade 1 inflammation) were observed [Figure 4]a and [Figure 4]b. Group 5 showed dilated and congested vessels and MCs in urothelium and lamina propria (average MC number = 6 with Grade 2 inflammation) [Figure 5]a and [Figure 5]b. Group 6 showed dilated and slightly congested vessels, MCs in urothelium and lamina propria, and multiple detached and vacuolated (average MC number = 5 with Grade 1 inflammation) [Figure 6]a and [Figure 6]b. Group 7 showed minimal infiltration with normally appearing urothelium and few MCs (average MC number = 2–3 Grade 0.5 inflammation/non-inflammatory) [Figure 7]a and [Figure 7]b. Group 8 rats showed minimal infiltration with multiple detachments of urothelium and few MCs (average MC number = 3 with Grade 1 inflammation) [Figure 8]a and [Figure 8]b.
Figure 1: Group 1: (a) Normal histology of muscular layer (M), urothelium (U) and lamina propria (L) (H and E, ×200). (b) Normal histology with a limited number of mast cells (toluidine blue, ×200)

Click here to view
Figure 2: Group 2: (a) Multiple detachments of urothelium (white arrow) focal decrease in the urothelium cell layers disrupted lamina propria containing dilated blood vessels, vacuolated cells in the urothelium and leucocytes infiltration (H and E, ×200). (b) Multiple mast cells in lamina propria, loss of continuity in transitional epithelium and a focal decrease in the urothelium cell layers (toluidine blue, ×200)

Click here to view
Figure 3: Group 3: (a) Multiple sloughing and loss of continuity of mucosa with mast cells in the urothelium and lamina propria (H and E, ×200). (b) Loss of continuity and few mast cells in mucosa and lamina propria (toluidine blue, ×200)

Click here to view
Figure 4: Group 4: (a) Minimal inflammation in lamina propria with minute detachment and few mast cells in the urothelium (H and E, ×200). (b) Minimal inflammation with minute detachment and few mast cells in both urothelium and lamina propria (toluidine blue, ×200)

Click here to view
Figure 5: Group 5: (a) Mild infiltrations in lamina propria and detached mucosa with vacuoles (H and E, ×200). (b) Mast cells in urothelium and lamina propria and reduced cell layers of the urothelium (toluidine blue, ×200)

Click here to view
Figure 6: Group 6: (a) Dilated and congested vessels, mast cells in urothelium (white arrow) and lamina propria (H and E, ×200). (b) Extension of mast cell to mucosa and leucocyte infiltration in lamina propria (toluidine blue, ×200)

Click here to view
Figure 7: Group 7: (a) Dilated and slightly congested vessels, mast cells in urothelium and lamina propria, as well as multiple detached and vacuolated urothelium (H and E, ×200). (b) Mast cells in the disturbed lamina propria with sloughing and vacuolated cell layers of urothelium (toluidine blue, ×200)

Click here to view
Figure 8: Group 8: (a) A few mast cells and normally appeared mucosa (H and E, ×200). (b) Few mast cells and minimal infiltration with normally appeared urothelium (toluidine blue, ×200)

Click here to view



  Discussion Top


The present study investigated that the possibility of OE/JP extracts could minimize stress-induced cystitis in rats, by pretreatment of the extracts. The current work is the first experimental study planned to estimate whether the supplementation of leaves extract of OEsubsp. Cuspidata, JP, and the combination ofOEsubsp. Cuspidata and JP would have a protective effect against stress-induced cystitis with physiological disorders and histological harms in rats.

Various rodent models of cystitis [4],[5] and a naturally occurring feline IC model [6] showed increased MC counts and activation. These models were associated with inflammation and hyperalgesia in the pelvic region. These studies revealed MC involvement in neurogenic bladder inflammation and pain in cystitis.[7] The present study showed that the administration of extracts OEsubsp. Cuspidata, JP, and the combination ofOEsubsp. Cuspidata and JP for 2 weeks produced a significant decrease of serum ACTH and CRH levels. Histopathologically marked alterations of the urinary bladder structure with a notable decrease in MC number and activation were observed. The present work showed that the treatment of rats with OEsubsp. Cuspidata and JPleaves' extracts and their combination for 2 weeks attenuated the physiological and histopathological changes in the urinary bladder of rats induced by water-immersion stress. This indicated the effectiveness of these extracts in the prevention of stress-induced cystitis. The main ingredient of the olive leaves is oleuropein, one of secoiridoid monoterpenes, which is thought to be responsible for pharmacological effects. Furthermore, the olive leaves contain triterpenes (oleanolic and maslinic acid), flavonoids (e.g., luteolin, apigenin, rutin), and chalcones.[24],[25] Due to its chemical composition, olive leaves are considered one of the most powerful innate antioxidants.

In vitro, oleuropein has high antioxidant activity compared to a hydrosoluble analog of tocopherol,[26] as do other constituents of olive leaves.[27] It was shown that total olive leaves' extracts had antioxidant activity more potent than Vitamin C and Vitamin E, due to the synergy between flavonoids, oleuropeosides, and substituted phenols.[8]

Other studies [15],[16] have evaluated the antioxidant properties of oleuropein on ethanol-induced oxidative damage and its beneficial effects on the liver function of Sprague Dawley male rats. They reported that oleuropein during ethanol treatment in rats resulted in higher antiperoxidative enzyme activity, catalase, and inhibited toxicity to the liver as monitored by the reduction in alanine aminotransferase and aspartate aminotransferase levels and thiobarbituric acid reactive substance concentration. They suggested that oleuropein possesses beneficial antioxidant effects against ethanol-induced liver toxicity.

Al-Attar et al.[14] investigated the influence of olive (OE) leaves extract on thioacetamide (TAA)-induced hepatic cirrhosis in Wistar male rats. They demonstrated that the extract of olive leaves possesses hepatoprotective properties against TAA-induced hepatic cirrhosis by inhibiting the physiological and histopathological alterations. Moreover, they suggested that the hepatoprotective effects of olive extract may be attributed to its antioxidant activity.

The petroleum ether fraction of JP showed significant hepatoprotective activity when investigated against CC14-induced liver injury in Wistar male rats.[28] The hepatoprotective activity was estimated throughout the quantification of biochemical parameters and confirmed by histopathology analysis. Different fractions obtained from the aerial parts of JPshowed significant activity as hepatoprotective when investigated against CC14-induced liver injury in Wistar male rats.[29] The hepatoprotective activity was evaluated through the quantification of biochemical parameters and confirmed using histopathological study.


  Conclusions Top


The most important findings in the current work are the observation that OEsubsp. Cuspidata and JPleaves' extracts and their combination were effective in attenuating stress-induced cystitis that was confirmed by biochemical analysis and histopathological examination. It may, therefore, be suggested from evidence in the current work that the supplementations of the OEsubsp. Cuspidata and JPleaves' extracts may give some beneficial results for IC. Moreover, this study suggests that the supplementation of these extracts may act by modulating stress hormones and could be used as excellent adjuvant support in the treatment of cystitis induced by stress. Finally, physiological, biochemical, and histopathological studies are needed to explore the exact mechanism of these extracts and their natural chemical constituents against other related pathogenic factors.

Acknowledgment

The authors gratefully acknowledged the college administration for providing the facility to work.

Financial support and sponsorship

This study was financially supported by the ICSR (Institute of Scientific Research and Revival of Islamic Heritage) at Umm Al-Qura University, Makkah, Saudi Arabia (Project ID: 43509010).

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardisation of terminology of lower urinary tract function: Report from the Standardisation Sub-Committee of the International Continence Society. Am J Obstet Gynecol 2002;187:116-26.  Back to cited text no. 1
    
2.
Bogart LM, Berry SH, Clemens JQ. Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: A systematic review. J Urol 2007;177:450-6.  Back to cited text no. 2
    
3.
Chung KH, Liu SP, Lin HC, Chung SD. Bladder pain syndrome/interstitial cystitis is associated with anxiety disorder. Neurourol Urodyn 2014;33:101-5.  Back to cited text no. 3
    
4.
Rudick CN, Bryce PJ, Guichelaar LA, Berry RE, Klumpp DJ. Mast cell-derived histamine mediates cystitis pain. PLoS One 2008;3:e2096.  Back to cited text no. 4
    
5.
Robbins M, DeBerry J, Ness T. Chronic psychological stress enhances nociceptive processing in the urinary bladder in high-anxiety rats. Physiol Behav 2007;91:544-50.  Back to cited text no. 5
    
6.
Westropp JL, Buffington CA.In vivo models of interstitial cystitis. J Urol 2002;167:694-702.  Back to cited text no. 6
    
7.
Klumpp DJ, Rudick CN. Summation model of pelvic pain in interstitial cystitis. Nat Clin Pract Urol 2008;5:494-500.  Back to cited text no. 7
    
8.
Benavente-Garcıa O, Castillo J, Lorente J, Ortuno A, Del Rio J. Antioxidant activity of phenolics extracted from Olea europaea L. leaves. Food Chem 2000;68:457-62.  Back to cited text no. 8
    
9.
Sato H, Genet C, Strehle A, Thomas C, Lobstein A, Wagner A, et al. Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea. Biochem Biophys Res Commun 2007;362:793-8.  Back to cited text no. 9
    
10.
Benavente-García O, Castillo J, Lorente J, Alcaraz M. Radioprotective effects in vivo of phenolics extracted from Olea europaea L. Leaves against X-ray-induced chromosomal damage: Comparative study versus several flavonoids and sulfur-containing compounds. J Med Food 2002;5:125-35.  Back to cited text no. 10
    
11.
Dekanski D, Janićijević-Hudomal S, Tadić V, Marković G, Arsić I, Mitrović DM. Phytochemical analysis and gastroprotective activity of an olive leaf extract. J Serbian Chem Soc 2009;74:367-77.  Back to cited text no. 11
    
12.
Omar SH. Oleuropein in olive and its pharmacological effects. Sci Pharm 2010;78:133-54.  Back to cited text no. 12
    
13.
Samet I, Han J, Jlaiel L, Sayadi S, Isoda H. Olive (Olea europaea) leaf extract induces apoptosis and monocyte/macrophage differentiation in human chronic myelogenous leukemia K562 cells: Insight into the underlying mechanism. Oxid Med Cell Longev 2014;2014:927619.  Back to cited text no. 13
    
14.
Al-Attar AM, Alrobai AA, Almalki DA. Effect of Olea oleaster and Juniperus procera leaves extracts on thioacetamide induced hepatic cirrhosis in male albino mice. Saudi J Biol Sci 2016;23:363-71.  Back to cited text no. 14
    
15.
Alirezaei M, Dezfoulian O, Kheradmand A, Neamati S, Khonsari A, Pirzadeh A. Hepatoprotective effects of purified oleuropein from olive leaf extract against ethanol-induced damages in the rat. Iran J Vet Res 2012;13:218-26.  Back to cited text no. 15
    
16.
Friis I. Forests and Forest Trees of Northeast Tropical Africa: Their Natural Habitats and Distribution Patterns in Ethiopia, Djibouti and Somalia. Royal Botanic Gardens, Kew. Additional Series XV: HMSO; 1992.  Back to cited text no. 16
    
17.
Mujwah AA, Mohammed MA, Ahmed MH. First isolation of a flavonoid from Juniperus procera using ethyl acetate extract. Arab J Chem 2010;3:85-8.  Back to cited text no. 17
    
18.
Samoylenko V, Dunbar DC, Gafur MA, Khan SI, Ross SA, Mossa JS, et al. Antiparasitic, nematicidal and antifouling constituents from Juniperus berries. Phytother Res 2008;22:1570-6.  Back to cited text no. 18
    
19.
Burits M, Asres K, Bucar F. The antioxidant activity of the essential oils of Artemisia afra, Artemisia abyssinica and Juniperus procera. Phytother Res 2001;15:103-8.  Back to cited text no. 19
    
20.
Loizzo MR, Tundis R, Conforti F, Saab AM, Statti GA, Menichini F. Comparative chemical composition, antioxidant and hypoglycaemic activities of Juniperus oxycedrus ssp. Oxycedrus L. berry and wood oils from Lebanon. Food Chem 2007;105:572-8.  Back to cited text no. 20
    
21.
El Beyrouthy M, Arnold N, Delelis-Dusollier A, Dupont F. Plants used as remedies antirheumatic and antineuralgic in the traditional medicine of Lebanon. J Ethnopharmacol 2008;120:315-34.  Back to cited text no. 21
    
22.
Seca AM, Silva AM. The chemical composition of the Juniperus genus (1970-2004). Recent Progr Med Plants 2006;16:401-522.  Back to cited text no. 22
    
23.
Silva FG. Chemical-induced nephropathy: A review of the renal tubulointerstitial lesions in humans. Toxicol Pathol 2004;32 Suppl 2:71-84.  Back to cited text no. 23
    
24.
Meirinhos J, Silva BM, Valentão P, Seabra RM, Pereira JA, Dias A, et al. Analysis and quantification of flavonoidic compounds from Portuguese olive (Olea europaea L.) leaf cultivars. Nat Prod Res 2005;19:189-95.  Back to cited text no. 24
    
25.
Pereira AP, Ferreira IC, Marcelino F, Valentão P, Andrade PB, Seabra R, et al. Phenolic compounds and antimicrobial activity of olive (Olea europaea L. Cv. Cobrançosa) leaves. Molecules 2007;12:1153-62.  Back to cited text no. 25
    
26.
Speroni E, Guerra M, Minghetti A, Crespi-Perellino N, Pasini P, Piazza F, et al. Oleuropein evaluated in vitro and in vivo as an antioxidant. Phytother Res 1998;12:S98-100.  Back to cited text no. 26
    
27.
Briante R, Patumi M, Terenziani S, Bismuto E, Febbraio F, Nucci R. Olea europaea L. Leaf extract and derivatives: Antioxidant properties. J Agric Food Chem 2002;50:4934-40.  Back to cited text no. 27
    
28.
Alqasoumi SI, Abdel-Kader MS. Terpenoids from Juniperus procera with hepatoprotective activity. Pak J Pharm Sci 2012;25:315-22.  Back to cited text no. 28
    
29.
Alqasoumi SI, Farraj AI, Abdel-Kader MS. Study of the hepatoprotective effect of Juniperus phoenicea constituents. Pak J Pharm Sci 2013;26:999-1008.  Back to cited text no. 29
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
Conclusions
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed75    
    Printed10    
    Emailed0    
    PDF Downloaded20    
    Comments [Add]    

Recommend this journal