Objective: To gather the fragmented literature on ethnobotany, phytochemistry and in-vitro activities of medicinal plants of Pakistan being used against common infections caused by Staphylococcus aureus (S. aureus). Methods: A large number of published and unpublished research studies related to the ethnomedicinal, phytochemical and anti-S. aureus activity of medicinal flora of Pakistan published from 1990-2018 were reviewed using online bibliographic databases such as PubMed, Web of Science, Science Direct, ResearchGate and libraries. Results: S. aureus can cause many human ailments including endocarditis, staphylococcal scalded skin syndrome, septic arthritis, respiratory problems with an estimated infection rate of 25%-35% across the globe. This review comprised of 86 medicinal plants. Data showed that people mostly used leaves (50%) for the preparation of traditional medicines. Correlation analysis on the reviewed data revealed that methanolic extract concentrations of medicinal plants was highly significantly positive correlated (r=0.8; P<0.01) with the S. aureus zone of inhibitions. S. aureus reportedly showed complete resistant to the commonly used antibiotic erythromycin. Isolated compounds like altheahexacosanyl lactone, cinnamaldehyde, niloticane, gobicusin A, asparacosin A, muzanzagenin, isoagatharesinol, friedelin, inophynone and eugenol were active against S. aureus. This study provided in-vitro proof for the flora of Pakistan used against different infections caused by S. aureus. Conclusions: Antibacterial agents from natural sources could be more effective against bacterial pathogens and will be helpful in minimizing the adverse effects of synthetic drugs, and hence provides a base for the pharmaceutical industries.

Objective: To identify the preventive effect of Angelica gigas Nakai (A. gigas Nakai) extract in a benzalkonium chloride-induced dry eye model. Methods: A total of 28 mice were divided into 4 groups: 1) Normal group: mice received only saline; 2) positive control group: mice received an oral solution without A. gigas Nakai extract at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m.; 3) A. gigas Nakai extract (5 mg); 4) A. gigas Nakai extract (10 mg). Both group 3) and group 4) received an oral solution with A. gigas Nakai extract (either 5 mg/kg or 10 mg/kg) at 10:00 a.m. and 0.2% benzalkonium chloride eye drops at 2:00 p.m. After 14 d of follow-up, tear volume measurement and fluorescein staining were evaluated for the recovery effects on ocular surface. Histologic analysis was conducted by hematoxylin and eosin staining. Apoptosis on ocular epithelium layer was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Expression of TNF- α was also measured using western blot analysis. Results: An increase in both the tear volume and the sustained fluorescein staining scores was observed, demonstrating the preventive effects of A. gigas Nakai extract. Structure changes such as irregularity of the epithelial layer and corneal epithelial cell death were inhibited in the A. gigas Nakai extract groups. Expression of TNF- α moderately declined; however, its expression level was still higher, compared to the normal group. Conclusions: Results from the current study show the significant preventive effect of A. gigas Nakai extract in a mouse model of benzalkonium chloride-induced dry eye syndrome. Thus, A. gigas Nakai extract could be considered as an oral preventive agent for dry eye syndrome in the future.

Objective: To know whether the effect of interferon-induced protein with tetratricopeptide repeats (IFIT) 1 polymorphism influences the susceptibility of cerebral malaria outcome. Methods: Case-control association study was performed among 314 Thai patients (110 with cerebral malaria and 204 with uncomplicated malaria) infected with Plasmodium falciparum. Genotyping for five tag-single nucleotide polymorphisms of IFIT1 was performed by endpoint genotyping. Results: Genotype frequencies of all tag-SNPs (single nucleotide polymorphisms) showed no association with malaria outcome. However, C allele of rs11203109 was associated with the protection from cerebral malaria (OR=0.62, 95% CI=0.38-0.99, P=0.048). Two single nucleotide polymorphisms (rs5786868 and rs57941432) were in linkage disequilibrium with rs11203109. Conclusions: This suggests that our associated single nucleotide polymorphism (rs11203109) might be a genetic marker of cerebral malaria progression in the Thai population.

Objective: To evaluate the biomarkers of oxidative stress in herpes zoster patients compared with control subjects. Methods: This study compared the nitric oxide (NO), hydrogen peroxide (H₂O₂), malondialdehyde, uric acid, and bilirubin levels between 43 herpes zoster patients and 47 age-matched control subjects. The area under the curve of the receiver operating characteristic curve was performed to evaluate the final logistic regression model. Results: The significant differences were observed in the serum levels of NO, H₂O₂, and malondialdehyde between the case and the control groups (P<0.001). However, no statistical differences were found in both uric acid and bilirubin levels between the groups. Additionally, the raised oxidant biomarkers were strongly associated with increased disease severity (P<0.001). Multiple logistic regression analysis with the highest area under the curve [0.98 (95% CI 0.95-1.00)] and the minimum number of variables showed that high levels of NO (OR 1.24; 95% CI 1.061.46; P=0.008) and H₂O₂ (OR 1.25; 95% CI 1.09-1.43; P=0.001) were associated with herpes zoster. Conclusions: High levels of NO and H₂O₂ were observed in patients with herpes zoster. Increased NO and H₂O₂ levels might be associated with herpes zoster, which needs to be confirmed by further studies.

Objective: To describe the spanning 25 years data for the occurrence, magnitude, and trends regarding antimicrobial resistance of non-typhoidal Salmonella (NTS) isolated from non-immune travelers to Thailand participating in joint military operations. Methods: A total of 355 NTS isolates, obtained from 2 052 fecal samples from US soldiers deployed for military maneuvers in Thailand during 1988-2013, were examined for NTS serogroup/ serotypes and tested for antimicrobial susceptibility by disk diffusion to these 10 antibiotics: ampicillin, azithromycin (AZM), ciprofloxacin, colistin, gentamicin, kanamycin, nalidixic acid, streptomycin (STR), tetracycline (TET), and trimethoprim/sulfamethoxazole. Identified AZM-resistant NTS isolates were further evaluated for their minimal inhibitory concentration by the E-test method. Results: NTS infections accounted for 17.3% (355/2 052), including 11 serogroups and 50 different serotypes. The most prevalent serogroup was Salmonella group C2-C3 (35.8%, 127/355) followed by groups B (21.1%, 75/355) and C1 (18.6%, 66/355). Identified serotypes included Salmonella hadar (n=60), Salmonella rissen (n=45), and Salmonella blockley (n=34). Among the predominate serogroups, antimicrobial resistance was consistently high against TET (76.9%, 273/355) followed by STR (40.8%, 145/355). One Salmonella senftenberg isolate demonstrated decreased ciprofloxacin susceptibility. Most isolates (94.6%) were resistant to one or more antimicrobials, and the most common multidrug resistance was TET-STR-nalidixic acid (11.5%, 41/355). Conclusions: The prevalence of NTS serotypes and the growing magnitude of antibiotic resistant bacteria isolated from deployed US military in Thailand are documented from 1988-2013. This study demonstrates the antibiotic resistance profiles, highlighting the effectiveness of AZM that is a first-line treatment for travelers to Southeast Asia. AZM-resistant NTS isolates are periodically observed over a 25- year period. Hence, the ongoing surveillance and prevalence efforts are required to monitor NTS resistant strains causing further treatment failure.

Objective: To investigate the diuretic and renal effects of Silybum marianum L. and Cistus ladaniferus L. in normal rats. Methods: Four groups of rats were used in each experiment. The first group received water, the second group received Cistus ladaniferus L. extract (100 mg/kg b.wt), the third group received Silybum marianum L. extract (100 mg/kg b.wt), and the fourth group received furosemide (10 mg/kg b.wt). Variables including urine volume, plasma and urine sodium, potassium and creatinine, and creatinine clearance were measured. Two experiments were conducted. A single dose of each intervention was used and the variables were measured during 24 h, and the interventions were given daily for a total of 8 d and the variables were measured during various intervals. Results: The single dose of each plant extract increased urine volume at all-time intervals and increased urine sodium and potassium excretion without affecting plasma sodium and potassium (P<0.05). On the day 8 after daily administration, the plant extracts induced a significant diuresis and natriuresis without affecting serum electrolytes (P<0.05), while furosemide caused hypokalemia. Both plant extracts significantly increased creatinine clearance (P<0.05). Conclusions: Silybum marianum L. and Cistus ladaniferus L. increase creatinine clearance and have a significant diuretic effect without affecting serum electrolytes. Silybum marianum L. is more potent than furosemide or Cistus ladaniferus L.

Objective: To investigate the role of oxidative stress in human renal tubular epithelial cells (HK-2) induced by high glucose and the underlying signal pathway in vitro. Methods: MYPT1, pro-caspase-3, PGC-1α, and Drp1 protein expressions were measured by Western blot. MnSOD2, Drp1 and PGC-1α mRNA expressions were detected by real time PCR. Results: Results showed that high glucose significantly up-regulated the protein expressions of MYPT1, pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells; while Rho kinase inhibitor fasudil and ROCK1 siRNA inhibited protein expressions of pro-caspase-3 and the mRNA expression of MnSOD2 in HK-2 cells induced by high glucose. Importantly, fasudil and ROCK1 siRNA markedly inhibited the expressions of mitochondrial motor proteins Drp1 and mitochondrial gene PGC-1α in HK-2 cells induced by high glucose. Conclusions: Our findings suggest that Rho kinase signal pathway is involved in mitochondrial oxidative damage and apoptosis in high glucose-induced renal tubular epithelial cells by regulating mitochondrial motor proteins Drp1 and mitochondrial gene PGC-1α. Targeting Rho kinase signal pathway might be a potential strategy for the treatment of diabetic nephropathy.