Zahid Manzoor | Isra University (original) (raw)

Papers by Zahid Manzoor

JPMA. The Journal of the Pakistan Medical Association, 2015

To determine the levels of oxidant, antioxidant and serum enzymes in thalassaemic children receiv... more To determine the levels of oxidant, antioxidant and serum enzymes in thalassaemic children receiving multiple blood transfusions. The case-control study was done from February to August 2012, and comprised thalassaemic children receiving multiple blood transfusions at Allied Hospital, Ali Zeb Foundation, and the Thalassaemia Centre in Hilal-e-Ahmar Hospital, Faisalabad, Pakistan. Healthy subjects were also screened for any related disease condition that could prejudice the results. Blood samples were analysed for the values of total oxidant status, total antioxidant capacity, serum malondialdehyde, catalase, paraoxonase, arylesterase, glutathione peroxidase and ceruloplasmin. There were 180 children in the study; 90(50%) cases and 90(50%) controls. Of the cases, 48(53.3%) were under-weight while the weight of 42(46.7%) was in the normal range. The values of total oxidant status and total antioxidant capacity were significantly…

Mitogen-activated protein kinases (MAPKs) play critical regulatory roles in the production of th... more Mitogen-activated protein kinases (MAPKs) play critical regulatory roles in the production of the pro-inflammatory
cytokines and downstream signaling events which lead to inflammation. Inflammation is a primarily localized and
protective response of host against microbial infection. C ontrolled inflammation is beneficial and necessary for host
defense while uncontrolled inflammatory response results in inflammatory diseases such as septic shock, rheumatoid
arthritis and cancer. The MAPK family consists of three subfamilies; the extracellular signal-regulated kinases (ERKs),
the c-Jun N-terminal kinases (JNKs), and the p38 MAPKs. MA PKs are involved in transmitting extracellular signals to
nucleus which leads to gene regulation. In this review, we summarize the current knowledge of ERK1/2, JNKs, and p38
MAPK members and their roles in inflammation.

Murine caspase-11 is orthologus to human caspase-4 and caspase-5, and is required for the respons... more Murine caspase-11 is orthologus to human caspase-4 and caspase-5, and is required for the response to cholera toxin
B and infection with Escherichia coli, Citrobacter rodentium or Vibrio cholerae . Caspase-11 rather than caspase-1 is the
main offender involved in sepsis. Hence, caspase-11 plays an essential pro-inflammatory role in innate immune response
to bacterial infections.

Toll-like receptors are required for detection of pathogen-associated molecular patterns and play... more Toll-like receptors are required for detection of pathogen-associated molecular patterns and play critical roles in
protection of host from infection. Murine TLR13 was recently reported to be involved in recognition of bacterial 23S
ribosomal RNA sequence that is the binding site of different antibiotics.

Ehrlichia muris is a Gram-negative obligate intracellular bacterium belonging to ... more Ehrlichia muris is a Gram-negative obligate intracellular bacterium belonging to the family Anaplasmat-
aceae . It preferentially replicates inside macrophages by utilizing nutrients and processes of the host
cell. In the present article, we studied the effects of E. muris infection on cell death of bone marrow-
derived macrophages (BMDMs). Primary BMDMs were used for accessing E. muris-induced cell death,
pro-inflammatory cytokine production and Western blot analysis. Human embryonic kidney cell line
293T (HEK293T) was used to access nuclear factor-kappaB (NF-B) activity. BMDMs infected with E.
muris showed significant inhibition of cell death when compared to uninfected cells. E. muris infection
resulted in IB degradation, thus activation of NF-B. In NF-B reporter gene assay, the HEK293T cells
infected with E. muris exhibited robust NF-B-dependent luciferase activity in a bacterial dose-dependent
manner. Furthermore, E. muris-induced inhibition of BMDMs cell death was abolished in the presence
of MG132, a proteasome inhibitor that blocks NF-B activation. Taken together, the results suggest that
E. muris infection of BMDMs may have an inhibitory effect on cell death via a mechanism dependent on
NF-B activation.

Marine algae are rich sources of various biologically active compounds with potential pharmaceut... more Marine algae are rich sources of various biologically active compounds with potential pharmaceutical properties. In
the present study, we investigated the inhibitory effects of Plocamium telfairiae extract (PTE) on proinflammatory
cytokine production in bone marrow-derived macrophage (BMDMs) and dendritic cells (BMDCs). PTE pre-treatment
in LPS-stimulated BMDMs and BMDCs showed a strong inhibition on interleukin (IL)-12 p40, IL-6, and tumor necrosis
factor (TNF)-α production as compared to non-treated controls. PTE pre-treatment showed significant inhibition on
phosphorylation of mitogen-activated protein kinases and degradation of inhibitor of kappa B (IκBα). Taken together,
these results suggest that PTE may have potential anti-inflammatory property and hence, warrant further studies
concerning the potentials of PTE for medicinal purpose.

This study was an extension of our previous antiemetic work. Many researchers quoted Cynodone dac... more This study was an extension of our previous antiemetic work. Many researchers quoted Cynodone dactylon as anti emetic agent but none of them have provided strong pharmacological evidence for it, which drove us for its therapeutic evaluation. Crude aqueous rhizome extract of C. dactylon was evaluated for anti-emetic activity. Emesis was induced by the oral administration of copper sulphate, fresh aqueous extract of Brasica compestris while intravenous Cisplatin was used to induce emesis in fifteen days age chicks of either sex. The anti-emetic activity was determined by calculating the mean decrease in number of emesis in comparison to those of control and standards. C. dactylon (50 and 100 mg/kg body weight orally) showed remarkable emesis suppressant activity when compared with standard drugs chlorpromazine, domperidone and metoclopramide. Both the doses showed remarkable antiemetic activity.

Crude aqueous bark extract of Cinnamon loureiroi. was evaluated for anti-emetic potential. Eme... more Crude aqueous bark extract of Cinnamon loureiroi. was evaluated for anti-emetic potential.
Emesis was induced by the oral administration of copper sulphate and fresh aqueous extract
of Brassica compestris to male chicks of fifteen days age. The anti-emetic activity was
determined by calculating the mean decrease in number of retching in contrast with those of
control. Cinnamon (3 and 6 mg / kg body weight orally) showed anti-emetic activity when
compared with standard drugs Chlorpromazine , Domperidone and Metoclopramide. Both the
extracts, showed the antiemetic activity, highest (79.22% inhibition) and the lowest (58. 94 %
inhibition) in copper sulphate induced emesis and highest (81.91% ) and the lowest( 59.57%)
in Brassica compestris induced emesis .

Thuja occidentalis, Linn is a potent medicinal plant in the folk system of medicine.... more Thuja occidentalis, Linn is a potent medicinal plant in the folk system of medicine. Thuja occidentalis, Linn
belonging to family Cupressaceae,. In the present study the methanolic extracts of whole plant of Thuja occidentalis,
Linn were studied for their antipyretic activity by TAB (Typhoid) vaccine and PGE1 induced pyrexia in rabbits. In
TAB vaccine-induced fever, the fever was significantly reduced and the body temperature was normalized by
administration of 100 and 200 mg/kg dose orally and the activity was comparable to the reference drug
(Paracetamol). On the other hand, pyrexia induced by PGE1 was significantly reduced as compared to the standard
drug (Aspirin). This study has established the antipyretic activity of Thuja occidentalis, Linn and thus, justifies the
folkloric and ethnomedical uses of this plant for fever.

Crude aqueous bark extract of Cinnamon loureiroi. was evaluated for counter irritant activity. Ir... more Crude aqueous bark extract of Cinnamon loureiroi. was evaluated for counter irritant activity. Irritation was induced
by the clockwise frictional movement of fine sand paper to the ear of rabbits of average 1.5 kg body weight. The
counter-irritant activity was determined by calculating the mean decrease in redness and erythma with those of
control. cinnamon extract (25, 50, 75, 100µg / 10 ml) showed counter irritant when compared with standard drug
dexamethasone. All the extracts, showed the counter irritant activity. Highest (91.97% inhibition) and the lowest
(41.39 % inhibition) respectively.

Objective: To investigate the possible effect of multiple blood transfusions on different hormone... more Objective: To investigate the possible effect of multiple blood transfusions on different hormones with respect to age and sex in thalassemic children.
Methodology: An experimetnal study was conducted over 12 months in Allied Hospital, Ali Zeb Foundation, and Thalassemia centre in Hilal-e-Ahmar Hospital, Faisalabad. A total number of 80 children were included in this study. They were divided into two groups, containing forty β-thalassemic patients and forty healthy controls. Each group was further subdivided based on sex and age, so that in each subgroup there were ten subjects of same sex with age ranging from 0-5 years and 6-10 years. Blood samples from all the children were withdrawn and analyzed for serum hormones levels of triiodothyronine (T3), thyroxine (T4), testosterone, estradiol and progesterone. All the data was analyzed by using Statistical analysis of variance (ANOVA).
Results: The values of triiodothyronine (T3), thyroxine (T4), testosterone, and estradiol were significantly (p < 0.01) lower irrespective of age and sex in thalassemic children when compared to normal children. However, the progesterone level was significantly (p < 0.01) higher in thalassemic children than normal control.
Conclusions: Multiple blood transfusions induce various endocrinopathies in thalassemic children. Regular evaluation of oxidants and antioxidants status and hormones should be carried out in thalassemic patients during initial few years of life.

In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f P Ph ha ar rm ma a S Sc ci ie ... more In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f P Ph ha ar rm ma a S Sc ci ie en nc ce es s

Background: Multiple blood transfusions are the mainstay of thalassemic patients in order to comb... more Background: Multiple blood transfusions are the mainstay of thalassemic patients in order to combat the severe anemia. These frequent blood transfusions result in the excessive iron deposition, leading to multiple injuries to a variety of organs in the body. In response to these injuries, the levels of various enzymes are disturbed. The whole phenomena usually involve the interrelation of one parameter with some other. The present study aimed to estimate the levels of serum ferritin and hepatic enzymes and to find out any possible correlation between them in thalassemic patients receiving multiple blood transfusions. Methods: A total number of 90 thalassemic patients of both sexes ranging from 10-15 years, receiving multiple blood transfusions were included in the present study. Blood samples from all the patients were withdrawn and analyzed for the values of serum ferritin, hemoglobin and hepatic enzymes (serum alanine transaminase, serum aspartate transaminase, serum alkaline phosphatase). Pearson correlation coefficient was applied to observe correlation between serum ferritin level and hepatic enzymes. A P value of ≤0.05 was considered statistically significant.

In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f P Ph ha ar rm ma a S Sc ci ie ... more In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f P Ph ha ar rm ma a S Sc ci ie en nc ce es s ABSTRACT The wound healing activity of topically applied methanol extract of Lycopus europaeus was evaluated in wistar rat by excision wound model for a period of 12 days. The extract was prepared as ointment form (5 and 10% w/w) and applied on Wistar rats. Neomycin ointment 0.5%w/w was used as standard drug. The healing of the wound was assessed by the rate of wound contraction, period of epithelialisation, skin breaking strength. Both the ointments (5% and 10% w/w) of Lycopus europaeus extract promoted the wound-healing activity significantly when compared to the standard drug. High rate of wound contraction, decrease the period for epithelialisation, high skin breaking strength were observed in animals treated with 10% w/w extract ointment when compared to the control group of animals. So methanol extract of Lycopus europaeus in the form of 10% ointment promote wound-healing activity better than the former concentration, 5%. The result obtained from this study indicates that methanol extract of Lycopus europaeus accelerates the wound healing process by decreasing the surface area of the wound. The efficacy of this plant in wound healing may be due to its epithelization, thereby justifying the traditional claim.

$Research paper thumbnail of Pharmacological evaluation of Rumex vesicarius Linn leaf extract and fractions in rabbit gastrointestinal ailment$

The aqueous-methanolic leaf extract and fractions of the Rumex vesicarius L. (Rv.Cr) was evaluate... more The aqueous-methanolic leaf extract and fractions of the Rumex vesicarius L. (Rv.Cr) was evaluated for the possible presence of spasmogenic and spasmolytic constituents to rationalize its traditional uses in gastrointestinal disorders. In rabbit jejunum, R. vesicarius caused a dose-dependent (0.03 to 0.3 mg/ml) weak stimulatory effect on spontaneous contractions, followed by relaxation at the next higher dose (1 mg/ml). In the presence of atropine (0.03 µM), the spasmogenic effect was abolished and the relaxant effect was obtained at lower doses (0.1 to 1.0 mg/ml) shifting the dose response curves to the left. The spasmolytic effect on the spontaneous and K + -induced contractions in atropinized preparations was mediated at doses 0.03 to 1.0 mg/ml and 0.3 to 5 mg/ml, respectively which explained the involvement of calcium channel blocking (CCB) effect. The CCB effect was confirmed when pretreatment of the tissue with R. vesicarius produced a dose-dependent shift in the Ca ++ dose-response curves to the right in a similar manner as verapamil. Activity-directed fractionations revealed that the spasmolytic effect was concentrated in methanolic fraction, while spasmogenic activity in the aqueous fraction which was remarkably stronger than aqueous-methanolic extract. This data shows that the crude leaf extract of R. vesicarius L. contains spasmogenic and spasmolytic constituents mediating their effect through cholinergic and CCB actions, respectively, which explains its traditional use in the gastrointestinal disorders such as abdominal colics and cramps, constipation and diarrhea, gestroesophagial reflux disease and irritable bowel syndrome/inflammatory bowel disease.

Marine algae are rich sources of various biologically active compounds with potential pharmaceuti... more Marine algae are rich sources of various biologically active compounds with potential pharmaceutical properties. In the present study, we investigated the inhibitory effects of Plocamium telfairiae extract (PTE) on proinflammatory cytokine production in bone marrow-derived macrophage (BMDMs) and dendritic cells (BMDCs). PTE pre-treatment in LPS-stimulated BMDMs and BMDCs showed a strong inhibition on interleukin (IL)-12 p40, IL-6, and tumor necrosis factor (TNF)-α production as compared to non-treated controls. PTE pre-treatment showed significant inhibition on phosphorylation of mitogen-activated protein kinases and degradation of inhibitor of kappa B (IκBα). Taken together, these results suggest that PTE may have potential anti-inflammatory property and hence, warrant further studies concerning the potentials of PTE for medicinal purpose.

Sargassum muticum (S. muticum) is a brown edible alga and widely distributed in Korea. This repor... more Sargassum muticum (S. muticum) is a brown edible alga and widely distributed in Korea. This report was designed to evaluate the anti-inflammatory properties of apo-9′-fucoxanthinone (APO-9′) isolated from S. muticum on pro-inflammatory cytokine production. S. muticum extract (SME) exhibited significant inhibitory effects on pro-inflammatory cytokine production in bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs). APO-9′ pre-treatment in the CpG DNA-stimulated BMDMs and BMDCs showed a strong dose-dependent inhibitory effect on interleukin (IL)-12 p40, IL-6 and tumor necrosis factor (TNF)-α production with IC 50 values ranging from 5.31 to 13.79. It exhibited a strong inhibitory effect on the phosphorylation of ERK1/2 and on activator protein (AP)-1 reporter activity. APO-9′ pre-treatment exhibited significant inhibition of CpG DNA-induced production of inducible nitric oxide synthase. Taken

To evaluate the analgesic and anti-inflammatory effects of methanolic extract of Lycopus europaeu... more To evaluate the analgesic and anti-inflammatory effects of methanolic extract of Lycopus europaeus on experimental animal models. Methodology: The analgesic activity was evaluated by hot plate, acetic acid induced writhing and formalin induced writhing method in Swiss Albino mice divided into 4 different groups (control, standard diclofenac sodium and extract at two different doses of 250 and 500 mg/kg BW). The extract was also investigated for the anti-inflammatory effect on Long Evans rats using carrageenan induced rat paw edema method. For anti-inflammatory study, 24 rats were divided into 4 different groups each receiving either distilled water, standard drug or the extract at the doses of 250 and 500 mg/kg BW. Results: Phytochemical analysis of the extract revealed the presence of tannins, flavonoids and terpenoids. The extract elicited a highly significant (p<0.001) analgesic activity in a dose dependent manner on hot plate method, acetic acid induced writhing test and also on both the early and late phases of formalin test at the doses employed. In the hot plate method, the extract increased the reaction time of heat sensation to 60.81% and 66.52% at the doses of 250 and 500 mg/kg BW respectively while that of the standard drug was 57.40% at the 3rd hour of study. In acetic acid induced writhing test, the percent inhibition of writhing response by the extract was 62.87% and 70.66% at 250 and 500 mg/kg doses respectively (p<0.001) which were even better than the standard drug diclofenac sodium (50.30%). The extract also significantly inhibited the licking response at the dose of 500 mg/kg in both the early phase (55.11%, p<0.01) and the late phase (66.43%, p<0.01) of formalin test while the standard drug inhibited by 52.27% and 72.03%, respectively. The oral administration of the extract significantly (p<0.001) inhibited inflammatory response induced by carrageenan in a dose dependent fashion. The most prominent inhibition of 61.68% (250 mg/kg) and 73.65% (500 mg/kg) were observed at the 4th hour of study. Conclusion: The central and peripheral analgesic as well as anti-inflammatory effect of the methanolic extract of Lycopus europaeus may be due to the presence of various chemical constituents specially flavonoids, tannins, alkaloids or terpenoids. These experimental findings would further establish the scientific basis of the traditional uses of the plant in the management and/or control of pain as well as inflammatory conditions.

Aim: The present study was planned to investigate the possible antipyretic activity of methanolic... more Aim: The present study was planned to investigate the possible antipyretic activity of methanolic leaves extract of Rumex vesicarius against various protocols of experimentally induced pyrexia in rabbits.

JPMA. The Journal of the Pakistan Medical Association, 2015

$Research paper thumbnail of Pharmacological evaluation of Rumex vesicarius Linn leaf extract and fractions in rabbit gastrointestinal ailment$