Ethnobotanical assessment of antidiabetic medicinal plants in District Karak, Pakistan.

BACKGROUND: Diabetes is a leading health disorder and is responsible for high mortality rates across the globe. Multiple treatment protocols are being applied to overcome this morbidity and mortality including plant-based traditional medicines. This study was designed to investigate the ethnomedicinal status of plant species used to treat diabetes in District Karak, Pakistan. MATERIALS AND METHODS: A semi-structured survey was created to collect data about traditionally used medicinal plants for diabetes and other ailments. The convenience sampling method was applied for the selection of informants. The collected data was evaluated through quantitative tools like frequency of citation (FC), relative frequency of citation (RFC), informant consensus factor (FIC), fidelity level (FL), and use value (UV). RESULTS: A total of 346 local informants were selected for this research. Out of them, 135 participants were men and 211 participants were women. Overall 38 plant species belonging to 29 plant families were used to treat diabetes. The most dominant plant family was Oleaceae having 11 species. Powder form (19%) was the most recommended mode of preparation for plant-based ethnomedicines. Leaves (68%) were the most frequently used parts followed by fruit (47%). The highest RFC was recorded for Apteranthes tuberculata (0.147). The maximum FL was reported for Apteranthes tuberculata (94.4) and Zygophyllum indicum (94.11) for diabetes, skin, and wounds. Similarly, the highest UV of (1) each was found for Brassica rapa, Melia azedarach, and Calotropis procera. Based on documented data, the reported ailments were grouped into 7 categories. The ICF values range between 0.89 (diabetes) to 0.33 (Cardiovascular disorders). CONCLUSION: The study includes a variety of antidiabetic medicinal plants, which are used by the locals in various herbal preparations. The species Apteranthes tuberculata has been reported to be the most frequently used medicinal plant against diabetes. Therefore, it is recommended that such plants be further investigated in-vitro and in-vivo to determine their anti-diabetic effects.

Cytotoxic effects of extracts and isolated compounds from Ifloga spicata (forssk.) sch. bip against HepG-2 cancer cell line: Supported by ADMET analysis and molecular docking.

The purpose of this study was to determine the anticancer potential of Ifloga spicata (I. spicata) against HepG-2 cell line. To assess I. spicata cytoxicity, brine shrimp lethality and MTT assays were performed. In the brine shrimp bioassay, the ethyl acetate fraction had a significant impact with an IC50 of 10 µg/ml. The ethyl acetate and chloroform fractions inhibited HepG-2 cell line effectively (IC50 values 5.54 and 6.52 µg/ml, respectively). The isolated compound, heptadecyl benzoate inhibited growth significantly (IC50, 8.92 µg/ml) while methyl dihydroxybenzoate had modest activity (25.66 µg/ml) against the cell line. Both compounds displayed acceptable pharmacokinetic parameters in the ADME study. In the docking study, the methyl dihydroxybenzoate was involved in two hydrogen bonds with two different residues Thr830 and Asp831. The heptadecyl benzoate carbonyl oxygen exhibited a single hydrogen bond with Lys692. Both showed good interactions with the active site of the (EGFR) tyrosine kinase. Our findings suggest that I. spicata might be a viable source of anticancer natural agents. This discovery raises the prospect of the future development of a new medication for the treatment of liver cancer.

Use of Preoperative Submucosal Dexamethasone in Third Molar Surgery: A Step towards Improvement in Quality of Life.

BACKGROUND: Surgical removal of impacted mandibular third molaris one of the most common procedures performed by Oral surgeons globally. The objective of the study was to ascertain theefficacyof pre-operative administration of submucosal dexamethasone on post-operative sequelae insurgically extracted impactedmandibular third molar.It was adouble-blind randomized controlled clinical trialthat wasperformed inthe Department of Oral & Maxillofacial Surgery at Abbottabad International Dental Hospital, Abbottabad from March 2019 to March 2020. METHODS: A total of 150 patientsweredivided into two groups,each having 75 patients. Group A received a placebo after administrationof local anesthesia whereas,group B received 4mg submucosaldexamethasone. A post-operative visit was scheduled after 48 hours to evaluate pain, facial swelling,and Trismus. RESULTS: On the second postoperative day, the patients in the experimental group presented with significantly reduced pain, facial swelling,and trismus in comparison to the control group. CONCLUSION: Pre-operativeadministration of 4mg dexamethasone through the submucosal route is efficacious inthe reduction of post-operative pain, swelling,and trismus in mandibular third molarsurgerythus enabling the patient to return to daily life activities earlier.

In Silico, Cytotoxic and Antioxidant Potential of Novel Ester, 3-hydroxyoctyl -5- trans-docosenoate Isolated from Anchusa arvensis (L.) M.Bieb. Against HepG-2 Cancer Cells.

BACKGROUND: Cancer is one of the chronic health conditions worldwide. Various therapeutically active compounds from medicinal plants were the current focus of this research in order to uncover a treatment regimen for cancer. Anchusa arvensis (A. anchusa) (L.) M.Bieb. contains many biologically active compounds. METHODS: In the current study, new ester 3-hydroxyoctyl -5- trans-docosenoate (compound-1) was isolated from the chloroform soluble fraction of A. anchusa using column chromatography. Using MTT assay, the anticancer effect of the compound was determined in human hepatocellular carcinoma cells (HepG-2) compared with normal epithelial cell line (Vero). DPPH and ABTS radical scavenging assays were performed to assess the antioxidant potential. The Molecular Operating Environment (MOE-2016) tool was used against tyrosine kinase. RESULTS: The structure of the compound was elucidated based on IR, EI, and NMR spectroscopy technique. It exhibited a considerable cytotoxic effect against HepG-2 cell lines with IC50 value of 6.50 ± 0.70 µg/mL in comparison to positive control (doxorubicin) which showed IC50 value of 1.3±0.21 µg/mL. The compound did not show a cytotoxic effect against normal epithelial cell line (Vero). The compound also exhibited significant DPHH scavenging ability with IC50 value of 12 ± 0.80 µg/mL, whereas ascorbic acid, used as positive control, demonstrated activity with IC50 = 05 ± 0.15 µg/mL. Similarly, it showed ABTS radical scavenging ability (IC50 = 130 ± 0.20 µg/mL) compared with the value obtained for ascorbic acid (06 ± 0.85 µg/mL). In docking studies using MOE-2016 tool, it was observed that compound-1 was highly bound to tyrosine kinase by having two hydrogen bonds at the hinge region. This good bonding network by the compound might be one of the reasons for showing significant activity against this enzyme. CONCLUSION: Our findings led to the isolation of a new compound from A. anchusa which has significant cytotoxic activity against HepG-2 cell lines with marked antioxidant potential.

Cytotoxicity of Anchusa arvensis Against HepG-2 Cell Lines: Mechanistic and Computational Approaches.

BACKGROUND: Liver cancer is a devastating cancer with increasing incidence and mortality rates worldwide. Plants possess numerous therapeutic properties, therefore the search for novel, naturally occurring cytotoxic compounds is urgently needed. METHODS: The anticancer activity of plant extracts and isolated compounds from Anchusa arvensis (A. arvensis) were studied against the cell culture of HepG-2 (human hepatocellular carcinoma cell lines) using 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. Apoptosis was investigated by performing Acridine orange -ethidium bromide staining, styox green assay and DNA interaction study. We also used tools for computational chemistry studies of isolated compounds with the tyrosine kinase. RESULTS: In MTT assay, the crude extract caused a significant cytotoxic effect with IC50 of 34.14 ± 0.9 µg/ml against HepG-2 cell lines. Upon fractionation, chloroform fraction (Aa.Chm) exhibited the highest antiproliferative activity with IC50 6.55 ± 1.2 µg/ml followed by ethyl acetate (Aa.Et) fraction (IC50, 24.59 ± 0.85 µg/ml) and n-hexane (Aa.Hex) fraction (IC50 29.53 ± 1.5µg/ml). However, the aqueous (Aa.Aq) fraction did not show any anti-proliferative activity. Bioactivity-guided isolation led to the isolation of two compounds which were characterized as para-methoxycatechol (1) and decane (2) through various spectroscopic techniques. Against HepG-2 cells, compound 1 showed marked potency with IC50 6.03 ± 0.75 µg/ml followed by 2 with IC50 18.52 ± 1.9 µg/ml. DMSO was used as a negative control and doxorubicin as a reference standard (IC50 1.3 ± 0.21 µg/ml). It was observed that compounds 1-2 caused apoptotic cell death evaluated by Acridine orange -ethidium bromide staining, styox green assay and DNA interaction study, therefore both compounds were tested for molecular docking studies against tyrosine kinase to support cytotoxic activity. CONCLUSION: This study revealed that the plant extracts and isolated compounds possess promising antiproliferative activity against HepG-2 cell lines via apoptotic cell death.

Understanding impact of pre-dissolved polymers on dissolution behavior of soluble carbamazepine cocrystal.

Cocrystallization is a novel approach for tackling the lower solubility concerns when they can yield solution concentration a lot better than their corresponding parent drug in crystalline form. To get the actual solubility and dissolution gains offered by the cocrystals, phase changes in solution (dissolution) has to be interrupted. In current study, we selected commonly used polymers in order to study their effects on the super saturation of carbamezepine-succinic acid (CBZ-SUC) cocrystal during dissolution studies. To observe solid phase changes during dissolution in situ Raman spectroscopy was used. At the completion of each test the solid phase was analyzed by Fourier-transform infrared spectroscopy (FTIR) and powder X-Ray diffractometry. In polymers absence, no dissolution improvement was achieved by the cocrystal owing to its quick transformation to the stable carbamazepine dihydrate (CBZDH). Pre-dissolved PVP at 2% w/v concentration did not inhibit CBZ crystallization as a dihydrate, whereas at 0.025% w/v pre-dissolved hydroxypropyl methyl cellulose acetate succinate (HPMCAS) did stabilize the cocrystal in buffer solution (pH 6.8) for the course of time studied. This cocrystal stabilization resulted in enhanced CBZ solubility ( Ì´ 4fold) caused by cocrystal super saturation state. Seeding of this stable supersaturated state with 1% w/v CBZDH resulted in CBZ crystallization as dihydrate with ultimate loss of solubility advantage.

Evaluation and assessment of prescribing patterns in elderly patients using two explicit criteria based screening tools: (The PRISCUS list and STOPP/START criteria).

BACKGROUND & OBJECTIVES: Rational prescribing can prevent medication errors and the associated harm, especially in old age patients, as they are being frequently prescribed with drugs for various ailments. Moreover, polypharmacy is a common practice in them. Therefore, a significant threat of potential drug interactions and adverse effects exist. Current study focuses on assessment of Potentially Inappropriate Medication (PIM) in medication prescribed to old age patients. METHODS: It was a forty days, descriptive and observational study conducted from August 15th 2017 to September 25th 2017 in which prescriptions given to elderly patients were reimbursed for collecting various sets of information. In order to assess PIMs (in Pakistani Set-up), STOPP/START addition 2008 (including examples of misprescribing, overprescribing and under prescribing) and the PRISCUS list (misprescribing and overprescribing) was used. Statistical analysis of results was performed using SPSS version 20. RESULTS: One hundred forty six cases of PIMs (including incorrect prescribing, overprescribing and under prescribing) were detected. It included incorrect prescriptions 104, under prescription 28 and over prescriptions 14. NSAIDS accounted for most incorrect prescriptions followed by benzodiazepines. Mostly NSAIDS were used for myalgia, backache and rheumatoid disorders. CONCLUSION: Current findings highlighted Potentially Inappropriate Prescribing (PIP), particularly of NSAIDs and under prescribing of statins in cardiovascular diseases. Study findings suggest introducing pertinent interventions at the stages involved in prescribing, prescription review and its follow up to reduce the PIP and PIMs.

Giant Cementoblastoma Of Left Maxilla Involving A Deciduous Molar.

Cementoblastoma is a relatively rare benign tumour. The clinicopathologic features, radiological findings, treatment and prognosis are reported here in a 10-year-old girl who presented to us from Afghanistan. The tumor was managed surgically and the histopathology confirmed the diagnosis of cementoblastoma. There was no evidence of recurrence at one year of follow up.

Oral cancer via the bargain bin: The risk of oral cancer associated with a smokeless tobacco product (Naswar).

In the wake of smokeless tobacco (SLT) being advocated as a mean of tobacco harm reduction, it is pertinent to establish individual health risks associated with each SLT product. This case-control study was aimed at assessing the risk of oral cancer associated with a smokeless tobacco product (Naswar). The study was conducted from September 2014 till May 2015 in Khyber Pakhtunkhwa, Pakistan. Exposure and covariate information was collected through a structured questionnaire. Conditional logistic regression was used to calculate odds ratios (OR) along with their 95% confidence intervals (CI). 84 oral cancer cases (62% males) and 174 age- and sex-matched controls were recruited. Ever users of Naswar had more than a 20-fold higher risk of oral cancer compared to never-users (OR 21.2, 95% CI 8.4-53.8). Females had a higher risk of oral cancer with the use of Naswar (OR 29.0, 95% CI 5.4-153.9) as compared to males (OR 21.0, 95% CI 6.1-72.1). Based on this result, 68% (men) and 38% (women) of the oral cancer burden in Pakistan is attributable to Naswar. The risk estimates observed in this study are comparable to risk estimates reported by previous studies on other forms of SLT use and the risk of oral cancer in Pakistan. The exposure-response relationship also supports a strong role of Naswar in the etiology of oral cancer in Pakistan. Although still requiring further validation through independent studies, these findings may be used for smokeless tobacco control in countries where Naswar use is common.

Heavy metals content, phytochemical composition, antimicrobial and insecticidal evaluation of Elaeagnus angustifolia.

Elaeagnus angustifolia was analyzed for determination of metals, phytoconstituents, bactericidal, fungicidal and insecticidal effects and to explore its chemical and biological potential. The root, branches, leaves, stem bark and root bark parts of E. angustifolia were found to contain iron, lead, copper, cadmium, zinc, chromium, nickel and cobalt in different concentrations. Crude extract of Elaeagnus angustifolia (Ea.Cr) was tested positive for the presence of alkaloids, flavonoids, saponins and tannins. Ea.Cr and its fractions, n-hexane (Ea.Hex), ethyl acetate (Ea.EtAc) and aqueous (Ea.Aq) showed bactericidal activity against Escherichia coli and Staphylococcus aureus, while against Pseudomonas aeruginosa only Ea.Hex and Ea.EtAc were effective. When tested for antifungal effect, Ea.Cr exhibited fungicidal action against Aspergillus fumagatus, Ea.EtAc and Ea.Aq against Aspergillus flavis and Ea.EtAc against Aspergillus niger. Ea.Hex was active against all three fungal strains. The chloroform fraction (Ea.CHCl3) was found inactive against the used microbes. Ea.Cr, Ea.Hex, Ea.CHCl3, Ea.EtAc and Ea.Aq caused mortality of Tribolium castaneum and Ephestia cautella insects observed after 24 and 48 h of treatment. These data indicate that E. angustifolia exhibits different heavy metals and compound groups. Methanolic extract of E. angustifolia and its various fractions possess antibacterial, antifungal and insecticidal activities, which elucidate medicinal application of the plant.

FREQUENCY OF LINGUAL NERVE INJURY IN MANDIBULAR THIRD MOLAR EXTRACTION: A COMPARISON OF TWO SURGICAL TECHNIQUES.

BACKGROUND: Surgical removal of impacted mandibular third molar is associated with a number of complications including postoperative bleeding, dry socket, postoperative infection, and injury to regional nerves. Lingual nerve damage is one of the main complications. To prevent this complication different techniques had been used. Lingual flap reflection is one of these procedures in which lingual soft tissue is reflected and retracted deliberately, the nerve is identified and is kept out of the surgical field. The objective of this study was to evaluate a surgical technique for third molar removal which is associated with minimum frequency of lingual nerve damage. METHODS: A randomized controlled trial was performed. A total of 380 patients with impacted mandibular third molars were included in this study. Each patient was allotted randomly by blocked randomization to group A where procedure was performed by reflection and retraction of lingual flap in addition to buccal flap and group B where procedure was performed by retraction of buccal flap only. RESULTS: Lingual nerve damage occurred in 8.94% in Group A in which lingual flap retraction was performed but damage was reversible. In group B, 2.63% lingual nerve damage was observed and nature of damage was permanent. The difference was statistically significant (p=0.008). CONCLUSIONS: Lingual flap retraction poses 3.4 times increased risk of lingual nerve damage during extraction of mandibular third molar when lingual flap is retracted but the nature of damage is reversible.

Cytotoxic and phytotoxic actions of Heliotropium strigosum.

This study describes the cytotoxic and phytotoxic activities of the crude extract of Heliotropium strigosum and its resultant fractions. In brine shrimp toxicology assays, profound cytotoxicity was displayed by ethyl acetate (LD50 8.3 µg/ml) and chloroform (LD50 8.8 µg/ml) fractions, followed by relatively weak crude methanolic extract of H. strigosum (LD50 909 µg/ml) and n-hexane fraction (LD50 1000 µg/ml). In case of phytotoxicity activity against Lemna acquinoctialis, highest phytotoxic effect was showed by ethyl acetate fraction (LD50 91.0 µg/ml), while chloroform fraction, plant crude extract and n-hexane, respectively, caused 50%, 30.76 ± 1.1% and 30.7 ± 1.1% inhibitory action at maximum concentration used, that is, 1000 µg/ml. These data indicates that H. strigosum exhibits cytotoxic and phytotoxic potential, which explore its use as anticancer and herbicidal medicine. The ethyl acetate and chloroform fractions were more potent for the evaluated toxicity effects, thus recommended for isolation and identification of the active compounds.

1,1-Diphenyl,2-picrylhydrazyl free radical scavenging, bactericidal, fungicidal and leishmanicidal properties of Teucrium stocksianum.

In the present study, we evaluated the pharmacological and toxicological effects of Teucrium stocksianum. The crude extract of T. stocksianum (Ts.Cr) and its subsequent organic fractions: n-hexane (Ts.Hex), chloroform (Ts.CHCl3) and ethyl acetate (Ts.EtAc) exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with different potencies. Ts.EtAc was found to be most potent. Ts.Cr, Ts.Hex, Ts.CHCl3 and Ts.EtAc showed significant bactericidal activity against Escherichia coli, Staphylococcus aureus, Salmonella typhi, Shigella flexneri and Bacillus subtilis at their extent. Ts.Cr, Ts.Hex, Ts.CHCl3 and Ts.EtAc displayed fungicidal action against Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus and Fusarium solani at various minimum inhibitory concentrations. Ts.Cr and Ts.EtAc exhibited marked inhibition of Leishmania tropica growth, observed after 48 and 96 hrs of treatment. These data indicate that the T. stocksianum methanolic extract and its resultant fractions possess antioxidant, antibacterial, antifungal and antileishmanial activities. Thus, the present research unearths the scientific base for T. stocksianum medicinal application as antioxidant and antimicrobial agents.

Heavy metals analysis, phytochemical, phytotoxic and anthelmintic investigations of crude methanolic extract, subsequent fractions and crude saponins from Polygonum hydropiper L.

BACKGROUND: Polygonum hydropiper L decoctions are traditionally used in the treatment of various ailments including inflammation, dyspepsia, diarrhea, menorrhagia, hemorrhoids, helminthiasis and CNS disorders. Present study was undertaken to investigate P. hydropiper L. for heavy metals content, phytoconstituents, Phytotoxic and anthelmintic activities to explore its toxicological and pharmacological potentials and rationalize its ethnomedicinal uses. METHODS: Plant crude powder, methanolic extract, fractions and soil samples were analyzed for heavy metals using atomic absorption spectrophotometer. Qualitative phytochemical analysis of the plant extracts was carried out for the existence of alkaloids, flavonoids, glycosides, anthraquinones, saponins, terpenoids, sterols and tannins. Radish seeds phytotoxicity assay was used to study phytotoxic action of plant extracts. Pheretima posthuma and Ascaridia galli were used to study anthelmintic potential of the plant using albendazole and levamisole HCl as standard drugs. RESULTS: Plant crude powder, methanolic extract (Ph.Cr), its subsequent fractions; n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq), saponins (Ph.Sp) and soil samples were found to contain copper (Cu), iron (Fe), chromium (Cr), zinc (Zn), lead (Pb), nickel (Ni), cadmium (Cd) and lead (Pb) in different concentrations. In crude powder of the plant, heavy metals concentrations were within WHO specified limits, whereas different fractions and soil samples exhibited high metals content. Ph.Cr was tested positive for the presence of alkaloids, flavonoids, saponins, tannins, triterpenoids and anthraquinone glycosides. Among different fractions Ph.EtAc, Ph.Sp, Ph.Chf and Ph.Bt were most effective causing 89.32, 89.25, 86.68 and 85.32% inhibition of seeds in phytotoxicity assay, with IC50 values of 50, 60, 35 and 100 µg/ml respectively. In anthelmintic study, Ph.Sp, Ph.Chf, Ph.EtAc and Ph.Cr were most effective against P. posthuma at 10 mg/ml concentration with an average death time of 50, 64.67, 68.67 and 71 minutes respectively. Ph.EtAc, Ph.Chf and Ph.Aq were most effective against A. galli with average death time of 7, 9 and 10 min respectively at 1 mg/ml concentration. CONCLUSIONS: Our findings indicate that P. hydropiper contains different heavy metals and secondary metabolites. Different fractions exhibited phytotoxic and anthelmintic activites comparable to control drugs, thus provide pharmacological basis for ethnomedicinal uses of this plant.

Frequency of unerupted mandibular third molar in mandibular angle fractures.

BACKGROUND: Fractures of the mandibular angle are common and comprise 31% of all mandibular fractures. Multiple recent studies report a 2-3 fold increased risk for mandibular angle fractures when un-erupted mandibular third molars are present. The objective of this study was to assess the frequency of un-erupted mandibular third molar in mandibular angle fractures. METHODS: This cross-sectional study was conducted at the Department of Oral and Maxillofacial Surgery, Ayub Medical College, Abbottabad from April to October 2009. One hundred and two patients were included both from the outdoor and ward on consecutive non-probability sampling base. Data were recorded on a structured Performa and analysed using SPSS-16. RESULTS: A hemi-mandible containing un-erupted mandibular third molar was seen to have a 1.41 times the risk of mandibular angle fracture then a hemi-mandible containing an erupted mandibular third molar. CONCLUSION: The presence of unerupted mandibular third molar is associated with an increased risk for mandibular angle fracture.