The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies.

The renin-angiotensin-aldosterone system (RAAS), is an old system with new fundamental roles in cancer biology which influences cell growth, migration, death, and metastasis. RAAS signaling enhances cell proliferation in malignancy directly and indirectly by affecting tumor cells and modulating angiogenesis. Cancer development may be influenced by the balance between the ACE/Ang II/AT1R and the ACE2/Ang 1-7/Mas receptor pathways. The interactions between Ang II/AT1R and Ang I/AT2R as well as Ang1-7/Mas and alamandine/MrgD receptors in the RAAS pathway can significantly impact the development of cancer. Ang I/AT2R, Ang1-7/Mas, and alamandine/MrgD interactions can have anticancer effects while Ang II/AT1R interactions can be involved in the development of cancer. Evidence suggests that inhibitors of the RAAS, which are conventionally used to treat cardiovascular diseases, may be beneficial in cancer therapies.Herein, we aim to provide a thorough description of the elements of RAAS and their molecular play in cancer. Alongside this, the role of RAAS components in sex-dependent cancers as well as GI cancers will be discussed with the hope of enlightening new venues for adjuvant cancer treatment.

A Review of the Potential Benefits of Herbal Medicines, Small Molecules of Natural Sources, and Supplements for Health Promotion in Lupus Conditions.

The Latin word lupus, meaning wolf, was in the medical literature prior to the 1200s to describe skin lesions that devour flesh, and the resources available to physicians to help people were limited. The present text reviews the ethnobotanical and pharmacological aspects of medicinal plants and purified molecules from natural sources with efficacy against lupus conditions. Among these molecules are artemisinin and its derivatives, antroquinonol, baicalin, curcumin, emodin, mangiferin, salvianolic acid A, triptolide, the total glycosides of paeony (TGP), and other supplements such as fatty acids and vitamins. In addition, medicinal plants, herbal remedies, mushrooms, and fungi that have been investigated for their effects on different lupus conditions through clinical trials, in vivo, in vitro, or in silico studies are reviewed. A special emphasis was placed on clinical trials, active phytochemicals, and their mechanisms of action. This review can be helpful for researchers in designing new goal-oriented studies. It can also help practitioners gain insight into recent updates on supplements that might help patients suffering from lupus conditions.

Synthesis of 3-hydroxypyridin-4-one derivatives bearing benzyl hydrazide substitutions towards anti-tyrosinase and free radical scavenging activities.

Tyrosinase is a vital enzyme in the biosynthesis of melanin, which has a significant role in skin protection. Due to the importance of the tyrosinase enzyme in the cosmetics and health industries, studies to design new tyrosinase inhibitors have been expanded. In this study, the design and synthesis of 3-dihydroxypyridine-4-one derivatives containing benzo hydrazide groups with different substitutions were carried out, and their antioxidant and anti-tyrosinase activities were also evaluated. The proposed compounds showed tyrosinase inhibitory effects (IC50) in the 25.29 to 64.13 µM range. Among all compounds, 6i showed potent anti-tyrosinase activity with an IC50 = 25.29 µM. Also, the antioxidant activity of derivatives by using DPPH radical scavenging indicates an EC50 value between 0.039 and 0.389 mM. Molecular docking studies were performed to reveal the position and interactions of 6i as the most potent inhibitor within the tyrosinase active site. The results showed that 6i binds well to the proposed binding site and forms a stable complex with the target protein. Furthermore, the physicochemical profiles of the tested compounds indicated drug-like and bioavailability properties. The kinetic assay revealed that 6i acts as a competitive inhibitor. Also, for the estimation of the reactivity of the best compound (6i), the density functional theory (DFT) was performed at the B3LYP/6-31+G**.

Design, synthesis, in silico ADME, DFT, molecular dynamics simulation, anti-tyrosinase, and antioxidant activity of some of the 3-hydroxypyridin-4-one hybrids in combination with acylhydrazone derivatives.

Tyrosinase is the rate-limiting enzyme in synthesizing melanin. Melanin is responsible for changing the color of fruits and vegetables and protecting against skin photo-carcinogenesis. Herein, some of the hybrids of 3-hydroxypyridine-4-one and acylhydrazones were designed and synthesized to study the anti-tyrosinase and antioxidant activities. The diphenolase activity of mushroom tyrosinase using L-DOPA assayed the inhibitory effects, and the antioxidant activity was assessed using DPPH free radical. The synthesized derivatives were confirmed using 1H-NMR, 13C-NMR, IR, and Mass spectroscopy. Among analogs, compound 5h bearing furan ring with IC50=8.94 µM was more potent than kojic acid (IC50=16.68 µM). The pharmacokinetic profile of the compounds showed that the tested compounds had suitable oral bioavailability and drug-likeness properties. The molecular docking studies showed that compound 5h was located in the tyrosinase-binding site. Also, the molecular dynamics simulation was performed on compound 5h, proving the obtained molecular docking results. At the B3LYP/6-31 + G** level of theory, the reactivity descriptors for 5 g and 5h were investigated using DFT calculations. Also, IR frequency was calculated to verify DFT results with experimental data. The electrostatic potential energy of the surface and the HOMO and LUMO molecular orbitals were also studied. It agrees with experimental results that the 5h is a soft molecule and ready for chemical reaction with other interacting molecules.Communicated by Ramaswamy H. Sarma.

Pharmacological Approaches to Decelerate Aging: A Promising Path.

Biological aging or senescence is a course in which cellular function decreases over a period of time and is a consequence of altered signaling mechanisms that are triggered in stressed cells leading to cell damage. Aging is among the principal risk factors for many chronic illnesses such as cancer, cardiovascular disorders, and neurodegenerative diseases. Taking this into account, targeting fundamental aging mechanisms therapeutically may effectively impact numerous chronic illnesses. Selecting ideal therapeutic options in order to hinder the process of aging and decelerate the progression of age-related diseases is valuable. Along therapeutic options, life style modifications may well render the process of aging. The process of aging is affected by alteration in many cellular and signaling pathways amid which mTOR, SIRT1, and AMPK pathways are the most emphasized. Herein, we have discussed the mechanisms of aging focusing mainly on the mentioned pathways as well as the role of inflammation and autophagy in aging. Moreover, drugs and natural products with antiaging properties are discussed in detail.