IN VITRO ANTI-INFLAMMATORY ACTIVITY OF SYRINGIC ACID

Objective: The present study was carried out to investigate the in vitro anti-inflammatory activity of syringic acid (SA).  Methods: SA was tested for it's in vitro anti-inflammatory activity at different concentrations in protein denaturation, proteinase inhibition and human red blood cell (HRBC) membrane stabilization assay. The reference drugs used were aspirin and diclofenac sodium. Results: SA showed concentration-dependent inhibition of protein denaturation and proteinase activity with a half-maximal inhibitory concentration (IC50) value of 49.38±0.56 µg/ml and 53.73±0.27 µg/ml respectively. Heat-induced haemolysis was inhibited by SA with an IC50 value of 57.13±0.24 µg/ml. SA also inhibited the hypotonicity-induced haemolysis (IC50 value of 53.87±0.72 µg/ml). Conclusion: From the present study, we can conclude that SA possesses appreciable anti-inflammatory effect against denaturation of proteins, proteinase activity, and human red blood membrane stabilization assays. Further studies are required for determining the possible mechanisms behind its anti-inflammatory action

α-GLUCOSIDASE AND α-AMYLASE INHIBITORY ACTIVITY OF INDIGOFERA CORDIFOLIA SEEDS AND LEAVES EXTRACT

Objective: The present study was done to find out the anti-diabetic effect of Indigofera cordifolia seeds and leaves extract on intestinal α–glucosidase, α-amylase enzymes In-vitro. Methods: In-vitro α–glucosidase and α-amylase assays were performed in order to evaluate anti- diabetic potential of Indigofera cordifolia seeds and leaves extract. The dose depended inhibitory effect of aqueous and methanol extract of seeds and leaves was compared with standard acarbose. Results: α-Amylase inhibitory activity of aqueous extract of seeds and leaves was found to be 65.12% and 55.02% while methanol extract showed 85.59% and 83.40 % inhibition at 4 mg/ml, respectively. In α–glucosidase inhibitory assay the methanol extract of seeds and leaves show more maltase inhibition (IC50 = 2.57±0.29 and 3.47±0.87 mg/mL, respectively) than sucrase (IC = 50 2.73±0.11 and 3.71± 0.46 mg/mL, respectively), at the same time aqueous extract of seeds and leaves showed more maltase inhibition (IC50 = 3.30±0.94 and 5.97± 0.22 mg/mL, respectively) than sucrase inhibition (IC50 = 4.30±0.16 and 6.56±0.62 mg/mL, respectively). Acarbose (standard) showed more maltase inhibition (IC50 = 9.86±0.12 μg/mL) than sucrase (IC50= 46.46±1.5 μg/mL) and had 93.40% α-amylase inhibition at 50 μg/ml. Conclusion: Both the methanol and aqueous extract of I. cordifolia seeds and leaves showed strong inhibition against animal α-amylase and α-glucosidase enzyme

ATTENUATING EFFECT OF TRITERPENOID SAPONIN RICH FRACTION OF ACHYRANTHES ASPERA LINN. ON ACUTE AND CHRONIC INFLAMMATION IN EXPERIMENTAL RATS

Objective: Achyranthes aspera Linn. is used as a traditional remedy for the treatment of various inflammatory conditions in India. The present study was designed to investigate the anti-inflammatory activity of methanolic extract of Achyranthes aspera (AA) and its active fraction using bioassay guided fractionation.Methods: The dry whole plant of AA was extracted with methanol and then fractionated with different polarity of solvents. Bioactive petroleum ether fraction was re-fractionated into triterpenoid saponin rich (TSR) and non-saponin subfractions and tested for anti-inflammatory activity. The activity of TSR subfraction was evaluated against oxidative stress induced by carrageenan in rat paw tissues.Results: TSR fraction showed significant (p<0.05) inhibition of rat paw oedema volume. Moreover, TSR fraction was also found to attenuate carrageenan induced oxidative damage by improving antioxidant enzymes levels. Furthermore, TSR fraction inhibited both heat and hypotonicity induced haemolysis of erythrocytes in vitro. In addition, TSR fraction significantly (p<0.05) reduced the granuloma formation in cotton pellet-induced granuloma in rats.Conclusions: The present study indicates TSR is a potential therapeutic for the treatment of inflammation-associated disorders.Â

SAFETY ASSESSMENT OF L-DOPA AND HYOSCINE HYDROBROMIDE IN COMBINATION: ACUTE AND SUB-ACUTE ORAL TOXICITY STUDIES

Objective: To evaluate the safety of L-Dopa and hyoscine hydrobromide combination by determining its potential toxicity after acute and sub-acute oral administration in rats.Methods: The acute and sub-acute toxicity study was performed according to the Organisation for Economic Co-operation and Development (OECD) Guideline 423 and 407 respectively. The combination of L-dopa and hyoscine hydrobromide was administered at 5 times the upper limit of therapeutic dose of each drug which is 1200 mg/d for L-dopa and 0.75 mg/d for hyoscine hydrobromide for adult human being and which was converted to required dose for Wistar rats (3 males and 3 females).Results: The combination of L-dopa and hyoscine hydrobromide at 5 times the upper therapeutic dose produced no treatment-related signs of toxicity or mortality in any of the animals tested during 14 d of the study. In the repeated dose 28 d oral toxicity study, there was no significant difference in any of the assigned parameters between the control and all treatment groups.Conclusion: It is established that the combination therapy of L-dopa and hyoscine hydrobromide is safe at 5 times the upper limit of therapeutics dose of each drug.Â

EVALUATION OF REPEATED DOSE-90-DAY ORAL TOXICITY STUDY OF L-DOPA AND HYOSCINE HYDRBROMIDE COMBINATION IN RATS

Objective: The present study was done to evaluate repeated-dose 90-day oral toxicity studies of l-dopa and hyoscine hydrbromide combination in rats. Methods: Repeated-dose 90-day oral toxicity study was performed according to the Organisation for Economic Co-operation and Development (OECD) guidelines 408. In the present study, combination of L-dopa and hyoscine hydrobromide was administered at 5 times the upper limit of therapeutic dose of each drug which is 1200 mg per day for L-dopa and 0.75 mg per day for hyoscine hydrobromide for adult human being and which was converted to required dose for Wistar rats (5 males and 5 females).Results: The combination of L-dopa and hyoscine hydrobromide at 5 times the upper therapeutic dose produced no treatment-related signs of toxicity or mortality in any of the animals tested during 90 d of the study. The subchronic administration of the combination of L-dopa and hyoscine hydrobromide did not produce any significant difference in any of the assigned parameters between the control and all treatment groups.Conclusion: It is established that the combination of L-dopa and hyoscine hydrobromide therapy is safe on repeated dose 90-day oral toxicity at 5 times the upper limit of therapeutics dose of each drug.Â

EVALUATION OF IN VITRO CYTOTOXIC ACTIVITY OF PETROLEUM ETHER AND METHANOL EXTRACT OF MENTHA ARVENSIS (WHOLE PLANT) ON HUMAN CANCER CELL LINES

Objective: Mentha arvensis (MA) commonaly known as Mint or Pudina, belongs to the Lamiaceae family. It is an aromatic herb traditionally used as an antiseptic, antihelmintic, diuretic, digestive, expectorant and cardio tonic. The objective of the present investigation was to examine in vitro cytotoxic activity of crude whole plant extracts of MA. Methods: Crude extracts were prepared from whole dried plant of MA by Soxhlet apparatus, using solvents petroleum ether (60°- 80°) and methanol successively. In vitro cytotoxic activity of crude extracts was evaluated by Sulforhodamine B assay on three human cancer cell-lines of different tissues i.e. A-549 (lung), MCF-7 (breast) and COLO-205 (colon). Hemolytic activity of crude extracts of MA on human RBCs was also checked. Results: Methanol extract of MA was observed to be significantly more cytotoxic in dose dependent manner than Petroleum ether extract of MA with IC50 ranging from 120-165µg/ml for selected cell lines. Methanol and petroleum ether extracts of MA were found to have no hemolytic effect on RBCs suggesting membrane destabilization is not the mechanism of action for their cytotoxic activity. Conclusion: This study suggests potential anti-tumor activity of Mentha arvensis and a need for further studies to identify the active component/s and to understand their mechanism/s of action

Arzanol, a Potent mPGES-1 Inhibitor: Novel Anti-Inflammatory Agent

Arzanol is a novel phloroglucinol α-pyrone, isolated from a Mediterranean plant Helichrysum italicum (Roth) Don ssp. microphyllum which belongs to the family Asteraceae. Arzanol has been reported to possess a variety of pharmacological activities. However, anti-inflammatory, anti-HIV, and antioxidant activities have been studied in some detail. Arzanol has been reported to inhibit inflammatory transcription factor NFκB activation, HIV replication in T cells, releases of IL-1β, IL-6, IL-8, and TNF-α, and biosynthesis of PGE2 by potentially inhibiting mPGES-1 enzyme. Diversity of mechanisms of actions of arzanol may be useful in treatment of disease involving these inflammatory mediators such as autoimmune diseases and cancer. This review presents comprehensive information on the chemistry, structure-activity relationship, and pharmacological activities of arzanol. In addition this review discusses recent developments and the scope for future research in these aspects

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. Methods We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. Results Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19–1.94), wheeze (OR 1.37, 95% CI 1.16–1.63) and dyspnoea (OR 1.83, 95% CI 1.53–2.20), but not lower FVC (β=0.02 L, 95% CI −0.02–0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI −0.49–0.58%). Some findings differed by sex and gross national income. Conclusion At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.publishedVersio

Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study

The Burden of Obstructive Lung Disease (BOLD) study was established to assess the prevalence of chronic airflow obstruction, a key characteristic of chronic obstructive pulmonary disease, and its risk factors in adults (≥40 years) from general populations across the world. The baseline study was conducted between 2003 and 2016, in 41 sites across Africa, Asia, Europe, North America, the Caribbean and Oceania, and collected high-quality pre- and post-bronchodilator spirometry from 28 828 participants. The follow-up study was conducted between 2019 and 2021, in 18 sites across Africa, Asia, Europe and the Caribbean. At baseline, there were in these sites 12 502 participants with high-quality spirometry. A total of 6452 were followed up, with 5936 completing the study core questionnaire. Of these, 4044 also provided high-quality pre- and post-bronchodilator spirometry. On both occasions, the core questionnaire covered information on respiratory symptoms, doctor diagnoses, health care use, medication use and ealth status, as well as potential risk factors. Information on occupation, environmental exposures and diet was also collected

DIABETIC NEPHROPATHY - GENESIS, PREVENTION AND TREATMENT

Diabetic Nephropathy (DN) is the foremost reason of End Stage Renal Disease (ESRD) and a major cause of premature deaths amongst people with diabetes. It is one of the most common complications of diabetes mellitus (DM) and has majorly influenced patients' morbidity and mortality. About 50% of patients suffering from DM for more than 20 years develop this complication. The present review focuses on the global scenario of diabetic nephropathy and different molecular mechanisms involved in its pathogenesis i. e. increased formation of advanced glycation end products (AGEs), enhanced glucose flux into polyol and hexosamine pathways, activation of protein kinase C (PKC) and other proinflammatory transcription factors. This review also highlights the precautionary measures to be taken by people with diabetes along with the therapeutic interventions involving angiotensin converting enzyme (ACE) inhibitors, renin inhibitors, angiotensin receptor antagonists, aldosterone antagonists, protein kinase C inhibitors, mechanistic target of rapamycin (m-TOR) inhibitors, agents inhibiting plasminogen activator inhibitor-1 (PAI-1), advanced glycation end products inhibitors, anti-inflammatory agents and antioxidant agents