A Comprehensive Review on Pharmacological Activities of Pachypodol: A Bioactive Compound of an Aromatic Medicinal Plant Pogostemon Cablin Benth.

As is well known, plant products have been increasingly utilized in the pharmaceutical industry in recent years. By combining conventional techniques and modern methodology, the future of phytomedicines appears promising. Pogostemon Cablin (patchouli) is an important herb used frequently in the fragrance industries and has various therapeutic benefits. Traditional medicine has long used the essential oil of patchouli (P. cablin) as a flavoring agent recognized by the FDA. This is a gold mine for battling pathogens in China and India. In recent years, this plant has seen a significant surge in use, and approximately 90% of the world's patchouli oil is produced by Indonesia. In traditional therapies, it is used for the treatment of colds, fever, vomiting, headaches, and stomachaches. Patchouli oil is used in curing many diseases and in aromatherapy to treat depression and stress, soothe nerves, regulate appetite, and enhance sexual attraction. More than 140 substances, including alcohols, terpenoids, flavonoids, organic acids, phytosterols, lignins, aldehydes, alkaloids, and glycosides, have been identified in P. cablin. Pachypodol (C18H16O7) is an important bioactive compound found in P. cablin. Pachypodol (C18H16O7) and many other biologically essential chemicals have been separated from the leaves of P. cablin and many other medicinally significant plants using repeated column chromatography on silica gel. Pachypodol's bioactive potential has been shown by a variety of assays and methodologies. It has been found to have a number of biological activities, including anti-inflammatory, antioxidant, anti-mutagenic, antimicrobial, antidepressant, anticancer, antiemetic, antiviral, and cytotoxic ones. The current study, which is based on the currently available scientific literature, intends to close the knowledge gap regarding the pharmacological effects of patchouli essential oil and pachypodol, a key bioactive molecule found in this plant.

Hyperfunction variant rs708035 of interleukin 1 receptor-associated kinases 2 gene involved in the predisposition of leprosy infection.

BACKGROUND: Mycobacterium leprae (slow-growing bacteria) is the etiological agent for leprosy infection, which is a chronic granulomatous disease. Symptoms initiate with the loss of sensation in the affected areas, which can lead to severe injuries, cuts and burns. IRAK2 (interleukin-1 receptor-associated kinases 2) is reported to function in the regulation of the NFκB pathway. The frequency of the IRAK2 polymorphism (rs708035) was unknown in the Pakistani population. Therefore, the study was designed to identify the role of the rs708035 SNP (single nucleotide polymorphism) in susceptibility to leprosy. METHODOLOGY: The case-control study was designed, and participants were selected by Ridley-Jopling Classification. Blood samples from healthy individuals and patients were collected after ethical approval. Genomic DNA was extracted for the amplification of selected polymorphisms by tetra-primer amplification refractory mutation system polymerase chain reaction. The desired products were observed via agarose gel (2.5%) electrophoresis followed by data analysis using bioinformatics tools (SNP Stats and SHEsis) and statistical tests (odds ratio, OR, and chi square). RESULTS: The study revealed that the mutant genotype (TT) was found to be frequent among cases (22.80%) in comparison with the controls (1.66%). The SNP rs708035 was significantly associated with the progression of leprosy (χ2  = 17.62, p < 0.0001). The targeted SNP significantly increases the risk of leprosy 2.3 times (OR = 2.3119, 95% CI 1.2729-4.1989, p < 0.01). The genetic model also confirms the significant association of the A/T genotype with leprosy in the over-dominant model (OR = 2.83, 95% CI 1.16-6.89, p < 0.001). CONCLUSIONS: The study revealed a significant association of the targeted SNP with leprosy and provided baseline data regarding the association of rs708035. The current research could be utilized for the preparation of biomarkers by considering a larger sample size. HIGHLIGHTS: The patients suffering from leprosy faced various comorbidities, including hypertension and diabetes. The study reports for the first time a significant association of interleukin 1 receptor associated kinases 2 (IRAK2) single nucleotide polymorphism (SNP) rs708035 among the Pakistani population (Karachi). The current study provides baseline data to develop diagnostic biomarkers for early detection of leprosy.

Association of serum vitamin D levels and TaqIrs731236 among patients with hypertensive coronary heart disease.

The development of cardiovascular diseases (CVD) is influenced through multiple risk factor and hypertension. It may increase the risk of cardiac events, and has a significant impact when combined with other risk factors including low levels of vitamin D and genetic variations like single nucleotide variations (SNV) (TaqIrs731236) in vitamin D receptor (VDR) gene. Blood samples from 500 study participants gathered including 250 hypertensive coronary heart disease patients, 250 age and gender matched healthy controls. To isolate genomic DNA, conventional salting out procedure used followed by amplification of targeted variations through Amplification Refractory Mutation System- Polymerase Chain Reaction (ARMS-PCR) Assay. The amplicon consists of 148 base pairs which was visualized on 2 % agarose gel electrophoresis and confirmed by DNA sequencing. The compared clinical parameters including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), high density lipoproteins (HDL), low density lipoproteins (LDL), cholesterol, triglycerides found significantly different among patients when compared with controls (P < 0.001). The Vitamin D exhibited insufficient levels at different stages of hypertension which were statistically, found significantly associated among patients with hypertensive coronary heart disease showing compared to controls (P < 0.001). The genotype association SNV (TaqIrs731236) T > C showed significant association with hypertensive coronary heart disease compared to healthy controls (Chi-Square χ2 = 60.75 and P < 0.00001). Further, the odds ratio of allelic association for risk allele (C) showed the strength of association with risk of disease, which increases by 2.02 times(P = 0.01). The results suggest that (TaqIrs731236) T > C as genetic predisposition factor, may contribute to develop the risk of hypertensive coronary heart disease. Hypertension as a risk factor along with insufficient levels of vitamin D and SNV (TaqIrs731236) as genetic variations may have been an important contributor to disease risk of hypertensive coronary heart disease.

Single nucleotide polymorphisms (rs3736228 and rs4988321) in low-density lipoprotein receptor-related protein-5 gene with predisposition to rheumatoid arthritis.

BACKGROUND: LRP5 (Lipoprotein Receptor 5) is one of the representatives of the low-density lipoprotein receptors family that play a crucial role in the process of bone homeostasis and bone remodeling. The role of LRP5 single nucleotide polymorphisms (SNPs) rs3736228 and rs4988321 has been associated with the susceptibility to osteoporosis and bone fracture. The frequency of mentioned LRP5 SNPs is unknown among RA (Rheumatoid Arthritis) patients. The case-control study was designed to determine the association of targeted SNPs among RA patients. METHODOLOGY: Patients were selected by ACR/EULAR 2010 criteria. After ethical approval blood samples of patients and healthy individuals were collected. DNA was extracted from the whole blood followed by amplification of the targeted region by T-ARMS PCR (Tetra-primer Amplification Refractory Mutation System) obtained product was observed on agarose gel electrophoresis. The data were analyzed by statistical and bioinformatic tools. RESULTS: It was observed that the SNPs rs3736228 and rs4988321 showed significant association with the risk of RA [χ2 = 44, p =< 0.001, O.R 95 % CI = 2.495, (1.865 âˆ¼ 3.337), p =< 0.001] and [χ2 = 85, p =< 0.001, O.R 95 % CI = 2.05, (1.571 âˆ¼ 2.69), p =< 0.001] respectively. Haplotypes AT, GC, and GT were found to be significantly associated with the risk of RA. Furthermore, both SNPs were in 40 % LD (Linkage Disequilibrium). CONCLUSIONS: The study revealed that SNPs rs3736228 and rs4988321 were significantly associated with the increased susceptibility to RA. The study serves as the baseline data considering targeted SNPs and their association with the progression of the disease. The study might be utilized for the development of potential biomarker for diagnostic purposes and in the precision medicine approach.

Impact of GABAA receptor gene variants (rs2279020 and rs211037) on the risk of predisposition to epilepsy: a case-control study.

Epilepsy is one of the most common neurological disorders with the incidence rate higher in developing states. It is a multifactorial ailment in which genetic diversity along with other factors plays an important role. The objective of this study was to assess the involvement of different risk factors including single nucleotide polymorphisms (SNPs) present in GABRA1 (rs2279020) and GABRG2 (rs211037) genes with the susceptibility to epilepsy in the targeted population. Blood samples of 180 subjects were taken and genotyped through tetra-primer amplification refractory mutation system-polymerase chain reaction technique. The obtained demographic and genotypic data were analyzed through different statistical tools including χ2 (chi-square) test and odds ratio. Parental consanguinity and family history of seizures were observed in a considerable number of cases of this study along with residency in industrial areas. But, no association of rs2279020 (χ2 = 0.900, P = 0.638) and rs211037 (χ2 = 0.045, P = 0.832) was observed with predisposition to epilepsy. However, GG genotype of rs2279020 was observed more in female cases as compared to male cases. Furthermore, TG haplotype was observed to be associated with the increased risk of developing epilepsy (χ2 = 9.097; OR = 2.586; P = 0.002). Genetic models also showed no correlation of the targeted SNPs with the susceptibility to epilepsy. The outcomes of the present study suggested that neither rs211037 nor rs2279020 were associated with increased susceptibility to epilepsy in the targeted population.

Tetra-primers ARMS-PCR Based Association Analyses of Synonymous and Intronic Variants in the ADAM12 Gene with Susceptibility to Knee Osteoarthritis: A Case-Control Study.

Genetic variations in a disintegrin and metalloprotease 12 (ADAM12) gene may contribute to develop Osteoarthritis (OA) that is characterized by cartilage matrix degradation and osteophytes formation. Therefore, the aim of present study was to analyze the association between the ADAM12 gene variants and knee OA predisposition. Tetra-primers ARMS-PCR was employed, to genotype the ADAM12 gene polymorphisms (rs1044122 and rs1871054) in 400 knee OA patients and equal number of age-matched controls. The association between ADAM12 gene variants and OA susceptibility was estimated using the Chi-square, logistic regression, haplotypes and linkage analyses. A significant association of rs1044122 (genotype: χ2 = 18.94; P < 0.001, allele: χ2 = 19.10; P < 0.001) and rs1871054 (genotype: χ2 = 10.04; P = 0.007, allele: χ2 = 10.57; P = 0.001) was observed with increased OA susceptibility. The variant genotype of rs1044122 increased OA risk more than twice [odds ratio (OR) 2.20; P = 0.001] and the risk was higher in females (OR 2.43; P = 0.001). The variant genotype of rs1871054 was perceived to almost double the risk in females (OR 1.97; P = 0.003). Moreover, a significant association of rs1044122 and rs1871054 under the additive genetic model (P < 0.001 and P = 0.002, respectively) was observed. The targeted ADAM12 gene polymorphisms, showed significant association with knee OA susceptibility. Females harboring the polymorphisms might be at risk. Besides, the haplotype CC of rs1044122 and rs1871054 in the ADAM12 gene may double knee OA risk. These findings may help in determining the etiology of OA and recognizing the people at risk of developing knee OA.

Vitamin D receptor gene polymorphism TaqI (rs731236) and its association with the susceptibility to coronary artery disease among Pakistani population.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of mortality in Pakistan and also worldwide. Vitamin D receptor (VDR) regulates the transcription of many genes and has a significant impact on inflammation and the morphology of cardiac cells. Genetic variation in the VDR gene such as the TaqI polymorphism (rs731236) may have an impact that causes adverse effects. Accordingly, it is important to determine possible association of the TaqI polymorphism (rs731236) with CAD. METHODS: The study included blood samples from 1016 subjects: 516 from CAD patients and 500 from age- and gender-matched controls. Genomic DNA was extracted by standard salting out method. Targeted variation was amplified by an allele-specific polymerase chain reaction (PCR). PCR products were examined and genotyped on agarose gel electrophoresis represented by an amplified product size of 148 bp followed by Sanger sequencing to validate variations. RESULTS: Serum vitamin levels, as observed using enzyme-linked immunosorbent assay, were found to be insufficient in both CAD patients (20.52 ± 0.06 ng/ml) and controls (21.6981 ± 0.05 ng/ml). The TaqI polymorphism (rs731236) T>C was found to be significantly associated with CAD (p < 0.0001). The odds ratio showed that the risk increases by 1.8-fold with variant C allele. Dominant, co-dominant and over dominant genetic model analyses suggested that the TC genotype might be a risk factor involved in the possible association with susceptibility to CAD. CONCLUSIONS: The TaqI polymorphism (rs731236) in the coding region may affect the function of the receptor by altering the binding site, which might participate in an inflammatory response and increase the risk for developing susceptibility to CAD.

Stunting and associated factors in children of less than five years: A hospital-based study.

OBJECTIVES: To estimate frequency of stunting and associated factors in children aged less than five years in a tertiary care hospital of Lahore. METHODS: An Analytical cross-sectional study was conducted in Pediatrics Outpatient Department at Akhtar Saeed Trust Teaching Hospital, Lahore from December 2017 to July 2018. Two hundred children of ages under five years coming to outdoor for treatment of minor ailments were included after informed consent from their parents. Non-probability, convenient sampling technique was used to collect sample. Data collected and analyzed on SPSS version 19. To find out association of stunting with multiple qualitative variables, chi-square test was applied and p-value was fixed at ≤ 0.05 to be significant. RESULTS: Out of 200 children screened in OPD, 42 (21.0%) were found to be stunted. The total percentage of stunting in male children was 28 (66.6%) and in female children were 14 (33.3%). Stunting was significantly associate with male gender (p=0.047), joint family system (p=0.049), low literacy level in mothers (p=0.031), unvaccinated status (p=0.003) and history of bottle feeding (p=0.037). CONCLUSION: The frequency of stunting in children less than five years of age is 42 (21.0%). The significant risk factors associated with stunting were found as male gender (p= 0.047), joint family system (p=0.049), low maternal education (p=0.031), unvaccinated status(p=0.03).

Association between obesity and risk of knee osteoarthritis.

The study was designed to investigate the association between obesity and the risk of knee osteoarthritis, recruiting 400 knee osteoarthritis patients and an equal number of controls. After the informed consent, diagnosed patients from Jinnah Post Graduate Medical Centre, Karachi were included as "cases". Age-matched individuals without the disease were included as "controls". Sociodemographic data were taken from each participant. Characteristics were compared by odds ratio and chi-square using SPSS 20 software. Obesity (OR 3.29; 95% CI 2.40-4.51), female gender (OR 2.87; 95% CI 1.94-4.25) and family history (OR 3.61; 95% CI 2.69-4.85) were found to be significantly associated with osteoarthritis (p<0.001). Highest OR was found in case of stair climbing >10 flights/d (OR 6.08; 95% CI 4.16-8.89; p<0.001), whereas heavy lifting (>25 kg/d for > 4 hr) was observed as another major factor with OR of 5.24 (95% CI 3.54-7.75; p<0.001) that elevates the risk. The study concluded that obesity is significantly associated with osteoarthritis and obese individuals (BMI>25 kg/m2) are at high risk of disease development. Furthermore, family history, prolonged standing (>2 h/d for >1 yr), heavy lifting (>25 kg/d for > 4 hr), stair climbing (>10 flights/d) and sitting on the floor (>5 h/d) might also be associated with knee osteoarthritis.

ABCG8 polymorphisms and renal disease in type 2 diabetic patients.

BACKGROUND AND AIM: Sterols, bile acids and their receptors have been involved in diabetic nephropathy. The ATP-binding cassette transporters G5 and G8 (ABCG5 and ABCG8) play an important role in intestinal sterol absorption and bile acid secretion. The aim of our study was to assess the associations between two ABCG8 coding polymorphisms, T400K and D19H, and the incidence of renal events in type 2 diabetic subjects. METHODS: Participants were the 3137 French type 2 diabetic subjects with micro- or macro-albuminuria from the genetic substudy of the DIABHYCAR trial. The mean duration of follow-up was 4years. Renal events were defined as a doubling of serum creatinine concentration or end-stage renal disease at follow-up. We then used a second population (DIAB2NEPHROGENE) of 2140 type 2 diabetic patients for the purpose of validation. RESULTS: In DIABHYCAR, the 400K allele was significantly associated with a higher risk of incident renal events in a multiple adjusted model (HR: 1.75 [95% CI 1.20-2.56], P=0.003). This association was still significant after further adjustments for baseline values of estimated glomerular filtration rate and urinary albumin excretion. In the validation population, the 400K allele was associated with the prevalence of end-stage renal disease (OR=2.01 [95% CI 1.15-3.54], P=0.015). No significant association was found between the D19H polymorphism and the risk of diabetic nephropathy. CONCLUSIONS: A polymorphism of the sterol transporter ABCG8 has been associated with the prevalence of end-stage renal disease and with the incidence of new renal events in type 2 diabetic patients.