Kannan R.R. Rengasamy

Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations

The current study explores the antimycobacterial efficacy of lichen-derived psoromic acid (PA) against clinical strains of Mycobacterium tuberculosis (M.tb). Additionally, the inhibitory efficacy of PA against two critical enzymes associated with M.tb, namely, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), as drug targets for antituberculosis therapy were determined. PA showed a profound inhibitory effect towards all the M.tb strains tested, with minimum inhibitory concentrations (MICs) ranging between 3.2 and 4.1 µM, and selectivity indices (SIs) ranging between 18.3 and 23.4. On the other hand, the standard drug isoniazid (INH) displayed comparably high MIC values (varying from 5.4 to 5.8 µM) as well as low SI values (13.0–13.9). Interestingly, PA did not exhibit any cytotoxic effects on a human liver hepatocellular carcinoma cell line even at the highest concentration tested (75 µM). PA demonstrated remarkable suppressing propensity against UGM compared to standard uridine-5-diphosphate (UDP), with 85.8 and 99.3% of inhibition, respectively. In addition, PA also exerted phenomenal inhibitory efficacy (half maximal inhibitory concentration (IC50) value = 8.7 µM, and 77.4% inhibition) against TBNAT compared with standard INH (IC50 value = 6.2 µM and 96.3% inhibition). Furthermore, in silico analysis validated the outcomes of in vitro assays, as the molecular interactions of PA with the active sites of UGM and TBNAT were unveiled using molecular docking and structure–activity relationship studies. Concomitantly, our findings present PA as an effective and safe natural drug plausible for use in controlling tuberculosis infections.

The role of flavonoids in autoimmune diseases: Therapeutic updates

ABSTRACT Flavonoids are natural polyphenolic compounds which are included in a panoply of drugs and used to treat and/or manage human ailments such as metabolic, cardiovascular, neurological disorders and cancer. Thus, the purpose of this review is to emphasize the importance of flavonoids for the treatment of autoimmune diseases and put into the limelight of the scientific community several health‐promoting effects of flavonoids which could be beneficial for the development of novel drugs from natural products. Despite available reviews on flavonoids targeting various disease conditions, a comprehensive review of flavonoids for autoimmune diseases is still lacking. To the best of our knowledge, this is the first attempt to review the potential of flavonoids for autoimmune diseases. The structure‐activity relationship of flavonoids in this review revealed that the rearrangement and introduction of other functional groups into the basic skeleton of flavonoids might lead to the development of new drugs which will be helpful in relieving the painful symptoms of various autoimmune diseases.

Chemical profile, antioxidant, and enzyme inhibitory properties of two Scutellaria species: S. orientalis L. and S. salviifolia Benth

This study investigates into the biological effects of solvent extracts (ethyl acetate, methanol, and water) of Scutellaria orientalis L. and Scutellaria salviifolia Benth. based on its enzyme inhibitory activity and antioxidant ability together with the screening of bioactive compounds.

In Vitro Study of Multi-Therapeutic Properties of Thymus bovei Benth. Essential Oil and Its Main Component for Promoting Their Use in Clinical Practice

Thymus bovei Benth. (TB) is an important plant in the traditional medicine of the Mediterranean region. This study investigates the health-promoting properties of TB essential oil (TB-EO) for its possible use in clinical practice with regards to its cytotoxic, anti-herpes simplex virus type 2 (HSV-2), and antihypertensive (through inhibition of human angiotensin-converting enzyme; ACE) properties. The phytochemical profile of EO (99.9%) was analyzed by Gas Chromatography with Flame-Ionization Detection (GC-FID) and Gas Chromatography-Mass Spectrometry (GC-MS). In this study, all biological methods were performed at the level of in vitro studies. The results showed that TB-EO exerted remarked cytotoxic properties against human cervical carcinoma cells, colon cancer cells, and lung adenocarcinoma cells with the half-maximal inhibitory concentration (IC50) values of 7.22, 9.30, and 8.62 µg/mL, respectively, in comparison with that of standard anticancer drug cisplatin with IC50 values of 4.24, 5.21, and 5.43 µg/mL, respectively. Fascinatingly, TB-EO showed very weak cytotoxicity on the healthy human fetal lung fibroblast cells with an IC50 value of 118.34 µg/mL compared with that of cisplatin (IC50 = 10.08 µg/mL). TB-EO, its main component geraniol, TB-EO combined with acyclovir (ACV) along with standard ACV, have displayed pronounced inhibitory properties against the replication of HSV-2 with the half-maximal effective concentration (EC50) values of 2.13, 1.92, 0.81 and 1.94 µg/mL, respectively, with corresponding selectivity indices (SI) 98.59, 109.38, 259.26 and 108.25, respectively. TB-EO and geraniol at a concentration of 15 µg/mL showed prominent inhibitory activities against ACE with % of inhibition 95.4% and 92.2%, respectively, compared with that of standard inhibitor captopril (99.8%; 15 µg/mL). Molecular docking studies were performed to unveil the mechanism of action of geraniol as well as structural parameters necessary for anti-HSV-2 activity (through the inhibition of HSV-2 protease) and ACE inhibition. This is the first report on the chemical composition of Egyptian TB-EO along with the above-mentioned biological activities. Our results may be considered as novel findings in the course of a search for new and active anticancer, anti-HSV-2 and antihypertensive agents, and expand the medicinal value of this plant and its phytochemicals in clinical practice.

Tanshinone IIA attenuates TNF-α induced PTX3 expression and monocyte adhesion to endothelial cells through the p38/NF-κB pathway

Tanshinone IIA is one of the most predominant bioactive constituents of Danshen, a traditional Chinese medicinal plant with multiple cardiovascular protective actions. Although Tanshinone IIA has been well documented for its endothelial protective efficacy, studies unveiling the mechanism and/or molecular targets for its pharmacological activity are still inadequate. In recent studies, it has been envisaged that the expression of pentraxin 3 (PTX3) was associated with atherosclerotic cardiovascular diseases (ACVD). Therefore, the current study was designed to evaluate the possible role of Tanshinone IIA in influencing the expression of PTX3 in endothelial cells and thereby prevents endothelial dysfunction. Molecular analyses through real-time PCR, western blot, and ELISA revealed that Tanshinone IIA down-regulates PTX3 gene expression as well as protein secretion in human endothelial cells in the presence or absence of TNF-α. Besides, Tanshinone IIA inhibits the adhesion of THP1 cells (a monocytic cell line) to activated-endothelial cells stimulated with TNF-α. Furthermore, mechanistic studies uncovered the role of p38 MAPK/NF-κB pathway in Tanshinone II-A mediated pharmacological effects. Thus, the present study exemplifies the manifestation of Tanshinone IIA as a plausible alternative natural remedy for ACVD by targeting PTX3.

Phytol: A review of biomedical activities

Phytol (PYT) is a diterpene member of the long-chain unsaturated acyclic alcohols. PYT and some of its derivatives, including phytanic acid (PA), exert a wide range of biological effects. PYT is a valuable essential oil (EO) used as a fragrance and a potential candidate for a broad range of applications in the pharmaceutical and biotechnological industry. There is ample evidence that PA may play a crucial role in the development of pathophysiological states. Focusing on PYT and some of its most relevant derivatives, here we present a systematic review of reported biological activities, along with their underlying mechanism of action. Recent investigations with PYT demonstrated anxiolytic, metabolism-modulating, cytotoxic, antioxidant, autophagy- and apoptosis-inducing, antinociceptive, anti-inflammatory, immune-modulating, and antimicrobial effects. PPARs- and NF-κB-mediated activities are also discussed as mechanisms responsible for some of the bioactivities of PYT. The overall goal of this review is to discuss recent findings pertaining to PYT biological activities and its possible applications.

Traditional and modern uses of onion bulb (Allium cepa L.): a systematic review

Abstract Onion, (Allium cepa L.), is one of the most consumed and grown vegetable crops in the world. Onion bulb, with its characteristic flavor, is the third most essential horticultural spice with a substantial commercial value. Apart from its culinary virtues, A. cepa is also used traditionally for its medicinal virtues in a plethora of indigenous cultures. Several publications have been produced in an endeavor to validate such traditional claims. Nonetheless, there is still a dearth of up-to-date, detailed compilation, and critical analysis of the traditional and ethnopharmacological propensities of A. cepa. The present review, therefore, aims to systematically review published literature on the traditional uses, pharmacological properties, and phytochemical composition of A. cepa. A. cepa was found to possess a panoply of bioactive compounds and numerous pharmacological properties, including antimicrobial, antioxidant, analgesic, anti-inflammatory, anti-diabetic, hypolipidemic, anti-hypertensive, and immunoprotective effects. Although a large number of in vitro and in vivo studies have been conducted, several limitations and research gaps have been identified which need to be addressed in future studies.

Combination of phenolic profiles, pharmacological properties and in silico studies to provide new insights on Silene salsuginea from Turkey

The genus Silene is renowned in Turkey for its traditional use as food and medicine. Currently, there are 138 species of Silene in Turkey, amongst which have been several studies for possible pharmacological potential and application in food industry. However, there is currently a paucity of data on Silene salsuginea Hub.-Mor. This study endeavours to access its antioxidant, enzyme inhibitory, and anti-inflammatory properties. Besides, reversed-phase high-performance liquid chromatography-diode array detector (RP-HPLC-DAD) was used to detect phenolic compounds, and molecular docking was performed to provide new insights for tested enzymes and phenolics. High amounts of apigenin (534u2009μg/g extract), ferulic acid (452u2009μg/g extract), p-coumaric acid (408u2009μg/g extract), and quercetin (336u2009μg/g extract) were detected in the methanol extract while rutin (506u2009μg/g extract) was most abundant in the aqueous extract. As for their biological properties, the methanol extract exhibited the best antioxidant effect in the DPPH and CUPRAC assays, and also the highest inhibition against tyrosinase. The aqueous extract was the least active enzyme inhibitor but showed the highest antioxidant efficacy in the ABTS, FRAP, and metal chelating assays. At a concentration of 15.6u2009μg/mL, the methanol extract resulted in a moderate decrease (25.1%) of NO production in lipopolysaccharide-stimulated cells. Among the phenolic compounds, epicatechin, (+)-catechin, and kaempferol showed the highest binding affinity towards the studied enzymes in silico. It can be concluded that extracts of S. salsuginea are a potential source of functional food ingredients but need further analytical experiments to explore its complexity of chemical compounds and pharmacological properties as well as using in vivo toxicity models to establish its maximum tolerated dose.