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Formulations of metronidazole M1, M2, M3, M4, and M5 with the polymer ethyl cellulose and M1*, M2*, M3*, M4* and M5* with the polymer Eudragit RS100 at varying concentrations were prepared and characterized by Zeta sizer, SEM, DSC, FTIR and XRD. The gel was evaluated for its spreadability, skin irritancy, entrapment efficiency and drug release. Size in M5* was 292.2 nm with PDI of 1.00 and in M2, 371.8 nm with PDI of 0.809 was observed. The entrapment efficiency and production yield with M5* was observed to be 68.40 % and 66.9 % respectively. While the EE and PY with M2 were 66.70 % and 58 % respectively. FTIR did not reveal any incompatibility between the polymer and the drugs and by SEM results, the shape of nanosponges appeared to be spherical and porous. 10% of the drug was released from nanosponges in Ist hour and almost 70 % in 8 hours.

Background: The human lips are the essential structure for speech, facial expression and oral functions like eating, drinking and breathing. The orthodontic treatment is very crucial for the advancement of the facial expression Lip incompetence is a condition in which the lips fail to close adequately leading to negative effects on speech, facial esthetics and oral functions. Study design: It is a retrospective study conducted at WATIM Dental College Rawat, Rawalpindi and Altamash Institute of Dental Medicine, Karachi for the duration of six months from Jan 2022 to June 2022. Material and Methods: The patients were divided into three groups. The patients that did not follow the inclusion criteria were excluded from the study. Group I had patients with competent lips, group II had patients with their lips apart and group III had incompetent lips. There were 45 patients in each group. Results: The length of group I members was 19.8 mm for men and 18.7 mm for women, which was less than group III individuals with 20 mm and 18.9 mm average upper lip length for males and females. Group II patients had a length of 17.5mm for male patients and 16.4 mm for female patients. The P-value was calculated and the results were statistically significant. Conclusion: The length of group I members was 19.8 mm for men and 18.7 mm for women, which was less than group III individuals with 20 mm and 18.9 mm average upper lip length for males and females. Group II patients had a length of 17.5mm for male patients and 16.4 mm for female patients. Keywords: Lip incompetence and competent lips.

Groundbreaking discoveries in molecular oncology have leveraged our understanding altogether to a new level. Mapping of plethora of cell signaling pathways has enabled researchers to drill down deep into the intermeshed regulatory networks which crosstalk to promote carcinogenesis and metastasis. More importantly, discovery of non-coding RNAs has added new layers of complexity to already complicated nature of cell signaling pathways. The discovery of circular RNAs (circRNAs) has opened the door to an ever-widening understanding of cellular processes that are controlled or influenced by circRNAs. In this review, we have summarized most recent advancements in our understanding related to interplay between circular RNAs and microRNAs for the regulation of NOTCH, Wnt/β-catenin, Hippo, SHH/GLI, JAK/STAT and TGF/SMAD pathways in different cancers.

Background: Diabetes Mellitus is increasing day by day due to comfort in daily life. So, there is an increase demand of the polyherbal formulations worldwide for the treatment of Diabetes Mellitus. So quality assurance of these products of great concern in developing countries like Pakistan. Methods: The PHFs were collected from the local market. Their quality control parameters, pharmacognostic evaluation, in vivo antidiabetic assay and oral glucose tolerance were evaluated and compared with standard drug metformin. Objectives: The objective of this study was phytochemical evaluation and Comparative evaluation of the antidiabetic activity of PHFs. Results: In the in vivo antidiabetic assay, the PHFs showed the time and dose dependent lowering in the blood glucose level of the alloxan (150mg/kg) rats at days 1, 4, 8, 12, 16 compared to the diabetic control group (p < 0.001). zubex, (PHF) showed maximum hypoglycemic effect at both doses (250,500 mg/kg). The ziabeen (PHF) cause the lowering in the blood glucose level but not in the significant way. Dawa-e-ajeeb ziabetees showed efficacy at the dose (500 mg/kg) not showed significant efficacy at dose (250 mg/kg). PHFs at 250,500 mg/Kg improved oral glucose tolerance overload in rats compared to hyperglycemic control group (p < 0.001), like metformin. Conclusion: It was concluded that tested PHFs were of standard quality control, while zubex have maximum antidiabetic activity compared to the standard drug.

The objectives of the current study were to estimate the out-of-pocket costs of illness of blood culture-confirmed typhoid fever, as well as to evaluate the different brands of ciprofloxacin HCl used in the treatment of typhoid fever. Therefore, a comparative study was designed for the assessment of costs of treatment at sixteen public (Government sector) and private tertiary health care hospitals located in Rawalpindi and Islamabad, Pakistan. On the basis of prescriptions collected from the hospitals, seven different brands of ciprofloxacin HCl prescribed in the treatment of typhoid fever were purchased from retail pharmacies for quality assessment. The mean costs for fourteen days and seven days treatment were analyzed and the overall costs of treatment were high at private health care sectors than public sectors. Model independent approach like similarity factor (f2) was also applied to assess the similarity between the dissolution profiles of different brands, and result indicated that three brands were found to be similar with reference product, while, three were dissimilar. It can be concluded that this cost-effective analysis of antibiotics used in the typhoid fever, will help to the local regularity body as well as WHO to update typhoid fever immunization recommendations. Ciprofloxacin was found an effective antibacterial agent in the treatment of typhoid fever and all brands met the pharmaceutical quality parameters. Thus, physicians, pharmacists and patients can select most appropriate quality brand for the therapy of typhoid fever.

Genetic, genomic and proteomic studies have refined our concepts related to underlying mechanisms of pancreatic cancer. Increasingly sophisticated knowledge has started to shed light on the fact that pancreatic cancer harbored multiple epigenetic and genetic alterations and revealed complicated and dense tumor microenvironments. Our rapidly evolving knowledge about pancreatic cancer has helped us in identification of myriad of underlying mechanisms which play instrumental role in disease onset, drug resistance and epithelial to mesenchymal transition (EMT). Additionally, loss of apoptosis is the cornerstone of cancer biology and researchers have devoted considerable attention to the versatile regulators involved in loss and restoration of apoptosis. Discovery of TNF/TNFR, FasL/Fas and TRAIL/TRAIL-R opened new horizons for detailed analysis of intracellular mechanisms regulated by these pro-apoptotic molecules. Decades of cutting-edge research helped in translation of TRAIL-based therapeutics into clinically effective therapeutics. In this review, we will focus specifically on groundbreaking achievements which have leveraged our concepts related to TRAIL-mediated signaling to yet another level. We will also discuss how basic and clinical scientists are making efforts to overcome the stumbling blocks associated with efficacy of TRAIL-based therapeutics against TRAIL-resistant pancreatic cancers. We partition this multi-component review into overview of the conceptual breakthroughs in regulation of TRAIL-mediated signaling in pancreatic cancers, push and pull between pro- and anti-apoptotic proteins to regulate TRAIL-mediated apoptosis and how researchers have identified different natural and synthetic molecules to restore apoptosis in TRAIL-resistant pancreatic cancer. We have also summarized how long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) regulated TRAIL-mediated apoptosis in pancreatic cancer. More importantly we will also set spotlight on the darker side of TRAIL/TRAIL-R pathway in pancreatic cancer. Circumstantial evidence highlighted cancer promoting role of TRAIL/TRAIL-R in pancreatic cancer. These diametrically opposed context-dependent roles of TRAIL-pathway are intriguing and need comprehensive research to address outstanding questions.

Purpose: To investigate the wound-healing potential of herbal formulations (emulgels and in situ gels) containing Saussurea lappa root extract (SLRE) via excision wound induction in albino rats. Methods: Preliminary phytochemical analysis of the methanol extract of roots of Saussurea lappa (SLRE) was performed using standard procedures. In vitro anti-inflammatory assay of SLRE was conducted using heat-induced hemolysis method at a concentration of 100 μg/mL. Acute toxicity of SLRE was also evaluated in mice at a single dose of 1000 mg/kg for 24 h. Emulgels and in situ gels were prepared using different concentrations of SLRE and assessed for their organoleptic and physical properties. In vitro drug release studies of the prepared formulations were carried out by Franz diffusion cell and the data fitted into various pharmacokinetic models. Wound healing was assessed using excision wound induction (380 mm2) on dorsal surface of male albino rats. Each formulation (F4, F5, F6, G1, G2 and G3) and pyodine gel (standard) were applied topically (0.5 g) for 20 days. Wound contraction was measured every fourth day. Results: SLRE showed 42.8 % inhibition in heat-induced hemolysis on erythrocyte membrane model, compared to aspirin (positive control). Moreover, SLRE did not cause mortality in mice at the given doses. All the formulations were stable after one month stability check at 40 °C for emulgels and at 25 °C for in situ gels. All the formulations followed first order drug release pattern. In situ gel (G3) exhibited better wound healing (100 ± 0.0028) than emulgel (F6, 99 ± 0.004) containing 5 g extract and standard pyodine gel (91 ± 0.014, p

Silver nanoparticles (AgNPs) have various applications in the biomedical field and are considered excellent microbicidal agents. Moreover, biological synthesis of AgNPs using medicinal plants further improves the medicinal applicability of these plants. In this study, the aqueous extract of Alocasia odora rhizome (RE) and Alocasia odora stem (SE) were used to synthesize stem aqueous extract-AgNPs (SNP) and rhizome aqueous extract-AgNPs (RNP). Furthermore, RNP and SNP were evaluated for their virucidal potential. The synthesis of SNP and RNP was monitored using a UV spectrophotometer by observing their surface plasmon resonance peak. In addition, scanning electron microscopy (SEM) gave further insight into their morphology and particle size, whereas energy-dispersive X-ray spectroscopy (EDX) confirmed the presence of silver ions. Interestingly, Fourier-transform infrared spectroscopy (FTIR) analysis of AgNPs revealed that phytomolecules acted as capping and stabilizing agents for SNP and RNP. The in vitro cytotoxicity of SNP and RNP was further analyzed using MTT assay on the U87-MG human glioblastoma cancer cell line and SNP found to be the most cytotoxic (43.40 µg/ml) among all. Besides that, SNP has also found to show the maximum cytopathic effects (CPE) against dengue virus type 2 (DENV-2) on Huh-7 cell line. As a result of the observations, it can be concluded that they can become a promising antiviral drug candidate and thus merit further testing. KEY POINTS: • AgNPs were successfully synthesized through Alocasia odora aqueous extract. • AgNPs were more cytotoxic on the U87-MG cell line than the extract alone. • AgNPs have shown significant reduction in the dengue viral infection than the extract alone.

Recent breakthroughs in high-throughput technologies have enabled the development of a better understanding of the functionalities of rho-associated protein kinases (ROCKs) under various physiological and pathological conditions. Since their discovery in the late 1990s, ROCKs have attracted the attention of interdisciplinary researchers due to their ability to pleiotropically modulate a myriad of cellular mechanisms. A rapidly growing number of published studies have started to shed light on the mechanisms underlying the regulation of ROCK1 and ROCK2 via long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in different types of cancer. Detailed analyses have suggested that lncRNAs may be characteristically divided into oncogenic and tumor suppressor lncRNAs. Several exciting recent discoveries have also indicated how different lncRNAs and circRNAs modulate ROCK1/2 and mediate multistep cancer onset and progression. The present review chronicles the major advances that have been made in our understanding of the regulatory role of ROCK1/2 in different types of cancer, and how wide-ranging lncRNAs and circRNAs potentiate ROCK-driven signaling by blocking the targeting activities of tumor suppressor microRNAs.

Purpose: To design parenteral in-situ gel of ceftriaxone using poloxamer as a thermosensitive agent, Carbopol as a pH-sensitive polymer and hydroxypropyl methylcellulose as a viscosity enhancer. Method: Lyophilized ceftriaxone was added in solution form to enhance its solubility and stability. Several formulations were designed using poloxamer (P 188, F 127 and P 407) and Carbopol (934P and 940) in varying concentrations, out of which an optimized formulation was chosen on the basis of its gelling capacity and respective transit time. Drug content uniformity, sterility and stability were studied. Drug-polymer and polymer-polymer interaction were determined by differential scanning calorimetry (DSC). Characterization of optimized formulation was carried out by Fourier transform infrared spectroscopy (FTIR). In-vitro release profile was determined by a modified Franz diffusion method. Results: Optimized formulation Q2 was characterized for various physicochemical parameters and found to be stable. In-vitro release study showed first order release pattern. DSC thermograms revealed that the polymers were compatible with each other as no physicochemical interactions were observed. The results were expressed as mean ± standard deviation (SD, p ≤ 0.05). Conclusion: Optimized formulation Q2 provided sustained release up to 10 days following first order release kinetics, and thus can be further developed for large-scale production.

Background and objectives: Breast cancer presents high morbidity among women with various treatment challenges. This study aims to evaluate the repurposed lamotrigine schiff base metal (LTG-SB-M) coordinates against in-vitro MCF-7 breast cancer cell lines and in-vivo N-methylnitrosourea (NMU)-persuaded toxicity of rats’ mammary gland. Method: In-silico computational analysis and in vitro cytotoxic studies on MCF-7 breast cancer cell lines was executed to build up the assumptions. In-vivo NMU-induced anticancer potential was assessed in forty Wistar rats; assigned into five groups of 8 rats each. Group I served as normal control and received normal saline, Group II received NMU (50 mg/kg), Group III received tamoxifen, whereas; Group IV and V received LTG-SB-M derivative (LAC3, LBC3) at dose of 100 mg/kg body weight, for 15 consecutive days. Intraperitoneal injection of NMU (single dose) was given at the age of 5, 9 and 13 weeks to the rats with the three week interval. For all experimental animals; biochemical markers were assessed. DNA strand breakage alongside the hormonal profile of estrogen and progesterone was also estimated. Results: All tested compounds present significant activity against MCF-7 cell lines in vitro and NMU-induced mammary tumor in vivo. The in vivo results of tested compounds present a significant decrease in weight of organ; with reinstated renal and hepatic enzymes. Histological analysis revealed strong countenance of proteins, estrogen, and progesterone in NMU-treated rats. Conclusion: These results suggest that LTG-SB-M complex can be used as better anticancer agent against breast cancer.

In search of suitable therapy for the management of Alzheimer’s disease, this study was designed to evaluate metal complexes against its biochemical targets. Zinc metal carboxylates (AAZ1–AAZ6) wer...

Epilepsy is the disease associated with seizures and convulsions. Various antiepileptic drugs have been used widely to treat these disorders. Lamotrigine [6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine] shows certain adverse effects at small doses, to evaluate its efficacy lamotrigine schiff based metal complexes were screened in-silico at voltage gated sodium channel for antiepileptic effect and dihydrofolate reductase enzyme for anticancer activity. Post docking analysis revealed that lamotrigine shows greater antiepileptic effect with its Schiff base complex of tin, with greater binding affinities on voltage gated sodium channel. However, anticancer effect of lamotrigine with its Schiff base silver complex shows highest binding affinity on dihydrofolate reductase enzyme. Study concluded that Schiff base derivative and its metal complexes express significant binding interactions with voltage gated sodium channel and dihydrofolate reductase enzyme.

With the recent technological advancements, a new golden era of natural products drug discovery has dawned. Increasingly it is being realized that structural modularity of many pharmacologically active products derived natural sources allows a building-block approach which can be exploited for analysis of regulation of deregulated oncogenic protein networks in different cancers. Piceatannol has been shown to effectively modulate JAK/STAT, Wnt/β-catenin, mTOR pathway in different cancers. In addition, certain hints have emerged which shed light on the regulation of microRNAs by piceatannol in some cancers. Regulation of deregulated oncogenic pathways by Piceatannol is gradually capturing attention and might be helpful in the multi-targeting of deregulated oncogenic networks in cancers.

Background Intensive care units (ICUs) are specialized units where patients with critical conditions are admitted for getting specialized and individualized medical treatment. High mortality rates have been observed in ICUs, but the exact reason and factors affecting the mortality rates have not yet been studied in the local population in Pakistan. Aim This study was aimed to determine rational use of antibiotic therapy in ICU patients and its impact on clinical outcomes and mortality rate. Methods This was a retrospective, longitudinal (cohort) study including 100 patients in the ICU of the largest tertiary care hospital of the capital city of Pakistan. Results It was observed that empiric antibiotic therapy was initiated in 68% of patients, while culture sensitivity test was conducted for only 19% of patients. Thirty-percent of patients developed nosocomial infections and empiric antibiotic therapy was not initiated for those patients (P

It is becoming progressively more understandable that pharmaceutical targeting of drug-resistant cancers is challenging because of intra- and inter-tumor heterogeneity. Interestingly, naturally derived bioactive compounds have unique ability to modulate wide-ranging deregulated oncogenic cell signaling pathways. In this review, we have focused on the available evidence related to regulation of PI3K/AKT/mTOR, Wnt/β-catenin, NF-κB and TRAIL/TRAIL-R by fisetin in different cancers. Fisetin has also been shown to inhibit the metastatic spread of cancer cells in tumor-bearing mice. We have also summarized how fisetin regulated autophagy in different cancers. In addition, this review also covers fisetin-mediated regulation of VEGF/VEGFR, EGFR, necroptosis and Hippo pathway. Fisetin has entered into clinical trials particularly in context of COVID19-associated inflammations. Furthermore, fisetin mediated effects are also being tested in clinical trials with reference to osteoarthritis and senescence. These developments will surely pave the way for full-fledge and well-designed clinical trials of fisetin in different cancers. However, we still have to comprehensively analyze and fully unlock pharmacological potential of fisetin against different oncogenic signaling cascades and non-coding RNAs. Fisetin has remarkable potential as chemopreventive agent and future studies must converge on the identification of additional regulatory roles of fisetin for inhibition and prevention of cancers.

In search of suitable therapy for the management of Alzheimer's disease, this study was designed to evaluate metal complexes against its biochemical targets. Zinc metal carboxylates (

Background Intensive care units (ICUs) are specialized units where patients with critical conditions are admitted for getting specialized and individualized medical treatment. High mortality rates have been observed in ICUs, but the exact reason and factors affecting the mortality rates have not yet been studied in the local population in Pakistan. Aim This study was aimed to determine rational use of antibiotic therapy in ICU patients and its impact on clinical outcomes and mortality rate. Methods This was a retrospective, longitudinal (cohort) study including 100 patients in the ICU of the largest tertiary care hospital of the capital city of Pakistan. Results It was observed that empiric antibiotic therapy was initiated in 68% of patients, while culture sensitivity test was conducted for only 19% of patients. Thirty-percent of patients developed nosocomial infections and empiric antibiotic therapy was not initiated for those patients (P

Three new bioactive metabolites, 1,6-dihydroxy- 2-methyl-heptan-4-one (1), 4-hydroxy-1-(2-methyl-oxiranyl)- pentan-2-one (2), and 2-(2-hydroxy-propyl)-4-methylfuran- 3-carboxylic acid amide (3) were isolated from the terrestrial Streptomyces sp. isolate ANK245, along with the new microbial constituent p-vinylanisol (4a) and the known metabolites p-vinyl-phenol (4b) and phenethyl alcohol. Analysis of the nonpolar part of the extract by gas chromatography/mass spectrometry (GC-MS) provided further evidence for tetradecanoic acid, 9-octadecenoic acid, hexadecanoic acid, 2-methoxy-4-vinylphenol (4c), 4-hydroxy-3-methoxy-benzaldehyde, o-hydroxybiphenyl, and 1,5,9-trimethyl-4,8,13-cyclotetradecatrien-1,3-diol (5). Structures 1–3 of the new compounds were elucidated by nuclear magnetic resonance (NMR) and NMR spectroscopy, but mass spectrometry (MS) techniques and their absolute configuration were determined by density functional theory (DFT) calculations and Mosher derivatisation. Their antimicrobial and cytotoxic activities were evaluated in comparison with the crude bacterial extract.

There has always been a keen interest of basic and clinical researchers to search for cancer therapeutics having minimum off-target effects and maximum anticancer activities. In accordance with this approach, there has been an explosion in the field of natural products research in the past few decades because of extra-ordinary list of natural extracts and their biologically and pharmacologically active constituents having significant medicinal properties. Apparently, luteolin-mediated anticancer effects have been investigated in different cancers but there is superfluousness of superficial data. Generalized scientific evidence encompassing apoptosis, DNA damage and anti-inflammatory effects has been reported extensively. However, how luteolin modulates deregulated oncogenic pathways in different cancers has not been comprehensively uncovered. In this review we have attempted to focus on cutting-edge research which has unveiled remarkable abilities of luteolin to modulate deregulated oncogenic pathways in different cancers. We have partitioned the review into various sections to separately discuss advancements in therapeutic targeting of oncogenic protein networks. We have provided detailed mechanistic insights related to JAK-STAT signaling and summarized how luteolin inhibited STAT proteins to inhibit STAT-driven gene network. We have also individually analyzed Wnt/β-catenin and NOTCH pathway and how luteolin effectively targeted these pathways. Mapping of the signaling landscape has revealed that NOTCH pathway can be targeted therapeutically. NOTCH pathway was noted to be targeted by luteolin. We have also conceptually analyzed how luteolin restored TRAIL-induced apoptosis in resistant cancers. Luteolin induced an increase in pro-apoptotic proteins and efficiently inhibited anti-apoptotic proteins to induce apoptosis. Luteolin mediated regulation of non-coding RNAs is an exciting and emerging facet. Excitingly, there is sequential and systematic accumulation of clues which have started to shed light on intricate regulation of microRNAs by luteolin in different cancers. Collectively, sophisticated information will enable us to develop a refined understanding of the multi-layered regulation of signaling pathways and non-coding RNAs by luteolin in different cancers.

Psoriasis is a common skin disease which is characterized by plaques and patches on the skin. Psoriasis is an autoimmune disease that involves T helper cells in the pathogenesis of the disease. Treatment of psoriasis is long term and not completely cures the disease. Plants have been extensively used in the treatment of different diseases so plants with anti-psoriatic activity have also been investigated. Results showed that Polypodium Decumanum, Wrightia Tinctoria, Cassia Tora and Givotia Rottleriformis Griff have significant activity in relieving symptoms of psoriasis.

Seven brands of ciprofloxacin (One multinational and six local) were evaluated in terms of their bioavailability and efficacy. Pharmaceutical Parameters like weight variation, hardness, disintegration, dissolution and content assay were determined. Antibacterial susceptibility assay was performed on standard Strain of Salmonella typhi (ATCC 14028). MIC and ZOI were assessed. The results of the study indicated that three local brands had content less than the stated claim of USP and one brand did not pass the disintegration and dissolution tests, so they cannot be used as therapeutic alternatives. Antibacterial assay showed less MIC value of the brands having greater drug content while drug with lesser amount had greater MIC value. Similarly, one local brand showed greater zone of inhibition (ZOI) as compared to multinational brand having more price than the local brand.

Purpose : To investigate the antihyperglycemic activity of Conyza canadensis via α-glucosidase inhibition in alloxan-induced diabetic mice. Methods : In vitro antidiabetic activity was investigated using α-glucosidase inhibition assay with acarbose (62.5, 125, 500 and 1000 μg/ml) as the standard drug. Conyza canadensis crude extract (Cc.Cr) in doses of 10, 30, 100 and 300 mg/kg were administered daily as a single dose to alloxaninduced (200 mg/kg) diabetic mice (Balb/c), and its effect on fasting blood glucose levels and body weight were evaluated for 15 consecutive days; oral glucose tolerance test was conducted. Metformin (500 mg/kg) was used as a standard antidiabetic drug for comparison. Acute toxicity of Cc.Cr was also evaluated at doses of 3 and 5 g/kg. Results : Conyza canadensis crude extract (Cc.Cr) exhibited strong enzyme inhibition at concentrations (μg/ml) of 1000 (74.78 ± 0.92), 500 (65.11 ± 0.07), 250 (57.55 ± 0.41), 125 (51.55 ± 0.67) and 62.5 ( 44.00 ± 0.57), with a median inhibitory concentration (IC 50 ) of 107 μg/ml. Cc.Cr at all test doses (10 - 300 mg / kg) reduced fasting blood glucose levels in alloxan (200 mg/kg) - induced diabetic mice on days 5, 10 and 15 compared to the diabetic control group (p < 0. 001). These effects were similar to those caused by the standard antidiabetic drug, metformin. Cc.Cr at all test doses also increased body weight of treated animals. The extract (300 mg/kg) significantly improved tolerance of oral glucose overload in mice, like metformin. The extract did not cause any mortality up to the maximum dose of 5 g/kg. Conclusion : The results reveal that Conyza canadensis possesses potent secondary metabolites which can cause inhibition of α-glucosidase. Moreover, the plant extract has the ability to reduce blood glucose level in diabetic animals and significantly improves oral glucose overload tolerance. Keywords : Conyza canadensis , α-Glucosidase, Blood glucose, Alloxan, Diabetes, Glucose tolerance

Purpose: To investigate the possible hepatoprotective potential of Parthenium hysterophorus crude extract (Ph.Cr) against carbon tetrachloride (CCL4)- and paracetamol-induced hepatotoxicity in rabbits.Methods: Twenty rabbits were divided into five groups of four rabbits each. Group 1 served as normal control and received normal saline (5 mL/kg). Group 2 received normal saline followed by CCL4 (0.75 mL/kg p.o dose) after 1 h. Groups 3 and 4 received Ph.Cr at doses of 15 and 30 mg/kg po, respectively, for 7 days followed by one dose of CCL4, 2 h after the last extract dose (0.75 mL/kg, sc). Group 5 received silymarin as reference standard at a dose of 100 mg/kg orally for 7 days followed by one dose of CCL4 (0.75 mL/kg, sc), 2 h after the last drug dose. The effect of the extract on potassium (K+)- induced contractions in isolated rabbit jejenum was also evaluated. At the end of the study, the animals were sacrificed and their liver architecture examined microscopically.Results: Pre-treatment of rabbits with Ph.Cr reduced ALT, ALP and TB levels (p < 0.05, p < 0.01, p < 0.001) dose dependently. Hepatoprotective data indicate that Ph.Cr markedly reduced CCL4- and paracetamol-induced toxicity by preserving the histological architecture of the liver tissue at near normal. In isolated rabbit jejunum tissue, Ph.Cr relaxed high K+ (80 Mm)-induced contractions in a concentration-dependent (0.03 - 10 mg/mL) manner like that caused by silymarin.Conclusion: In the light of the results obtained, Parthenium hysterophorous possesses hepatoprotective activity against CCL4- and paracetamol-induced hepatic damage, possibly mediated via its antioxidant and Ca++ antagonist mechanisms.Keywords: Parthenium hysterophorus, Toxins, Hepatoprotection, Ca++ antagonist, Silymarin