Syam Mohan

Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC₅₀ values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities (p < 0.05). The ROS level showed 1.3-fold increase (p < 0.05) at the low concentrations used and thus it was concluded that the compounds increased the ROS level eventually leading to apoptosis in MCF-7 cells through intrinsic as well as extrinsic pathways.

Over the past decades, various studies have highlighted the pure natural compound, α-mangostin as their main topic. The compound’s pre-clinical and pharmacological properties have been recognized and defined in these studies. α-Mangostin shows strong pharmacological effects in in vitro and in vivo model systems by targeting a number of vital cellular factors through various mechanisms of action. Despite its important molecular versatility, the α-mangostin still has limited clinical application. In order to optimize the conditions of this compound as a chemotherapeutic and chemopreventive agent, for instance in diseases such as cancer, obesity, diabetes as well as inflammatory disorders, the recent tendency is to limit the range of its pharmacological properties. The present work reviews recent studies on the central and potential pharmacological principles as well as the preclinical applications of the α-mangostin.

BACKGROUND: Gout is an inflammatory arthritis manifesting as acute episodes of severe joint pain and swelling, which can progress to chronic tophaceous or chronic erosive gout, or both. Here, we present the most up-to-date global, regional, and national estimates for prevalence and years lived with disability (YLDs) due to gout by sex, age, and location from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, as well as forecasted prevalence to 2050. METHODS: Gout prevalence and YLDs from 1990 to 2020 were estimated by drawing on population-based data from 35 countries and claims data from the USA and Taiwan (province of China). Nested Bayesian meta-regression models were used to estimate prevalence and YLDs due to gout by age, sex, and location. Prevalence was forecast to 2050 with a mixed-effects model. FINDINGS: In 2020, 55·8 million (95% uncertainty interval 44·4-69·8) people globally had gout, with an age-standardised prevalence of 659·3 (525·4-822·3) per 100 000, an increase of 22·5% (20·9-24·2) since 1990. Globally, the prevalence of gout in 2020 was 3·26 (3·11-3·39) times higher in males than in females and increased with age. The total number of prevalent cases of gout is estimated to reach 95·8 million (81·1-116) in 2050, with population growth being the largest contributor to this increase and only a very small contribution from the forecasted change in gout prevalence. Age-standardised gout prevalence in 2050 is forecast to be 667 (531-830) per 100 000 population. The global age-standardised YLD rate of gout was 20·5 (14·4-28·2) per 100 000 population in 2020. High BMI accounted for 34·3% (27·7-40·6) of YLDs due to gout and kidney dysfunction accounted for 11·8% (9·3-14·2). INTERPRETATION: Our forecasting model estimates that the number of individuals with gout will increase by more than 70% from 2020 to 2050, primarily due to population growth and ageing. With the association between gout disability and high BMI, dietary and lifestyle modifications focusing on bodyweight reduction are needed at the population level to reduce the burden of gout along with access to interventions to prevent and control flares. Despite the rigour of the standardised GBD methodology and modelling, in many countries, particularly low-income and middle-income countries, estimates are based on modelled rather than primary data and are also lacking severity and disability estimates. We strongly encourage the collection of these data to be included in future GBD iterations. FUNDING: Bill & Melinda Gates Foundation and the Global Alliance for Musculoskeletal Health.

Traumatic brain injury (TBI) is an important global health concern that represents a leading cause of death and disability. It occurs due to direct impact or hit on the head caused by factors such as motor vehicles, crushes, and assaults. During the past decade, an abundance of new evidence highlighted the importance of inflammation in the secondary damage response that contributes to neurodegenerative and neurological deficits after TBI. It results in disruption of the blood-brain barrier (BBB) and initiates the release of macrophages, neutrophils, and lymphocytes at the injury site. A growing number of researchers have discovered various signalling pathways associated with the initiation and progression of inflammation. Targeting different signalling pathways (NF-κB, JAK/STAT, MAPKs, PI3K/Akt/mTOR, GSK-3, Nrf2, RhoGTPase, TGF-β1, and NLRP3) helps in the development of novel anti-inflammatory drugs in the management of TBI. Several synthetic and herbal drugs with both anti-inflammatory and neuroprotective potential showed effective results. This review summarizes different signalling pathways, associated pathologies, inflammatory mediators, pharmacological potential, current status, and challenges with anti-inflammatory drugs.