Alleviating Neurodegenerative Diseases Associated with Mitochondrial Defects by Therapeutic Biomolecules.

Neurodegenerative diseases are emerging as a global health concern in the current sce-nario, and their association with mitochondrial defects has been a potential area of research. Mi-tochondria, one of the essential organelles of the cell, serve as the cell's powerhouse, producing energy and ensuring cellular health. Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Pelizaeus-Merzbacher disease have been found to be primarily triggered by mitochondrial malfunction. One of the key byproducts of mitochondrial respiration, reactive oxygen species, also contributes significantly to mitochondrial DNA muta-tions that eventually cause mitochondrial breakdown. This review paper comprehensively examines the potential of therapeutic biomolecules, specifi-cally mitochondria-specific antioxidants, in mitigating the impact of mitochondrial defects on neurodegenerative diseases. It provides a detailed analysis of the mechanisms involved in mito-chondrial dysfunction, the potential therapeutic targets of these biomolecules, and their structure-activity relationship information are also discussed in this review. Various research articles and publications were used extensively in compiling the data, and the structures of biomolecules were prepared using software such as ChemDraw and ChemSketch. Crucial elements triggering mitochondrial abnormalities were identified and a tabular compilation of bioactive antioxidant compounds along with their therapeutic targets, was presented. Mitochondria-specific antioxidant therapy is an innovative and promising strategy for the man-agement of neurodegenerative diseases associated with mitochondrial defects. This review pro-vides a thorough summary of the current state of research and promising avenues of research and development in this field, emphasizing the importance of further investigations and clinical trials to elucidate their therapeutic benefits.

An Insight into the Hepatoprotective Activity and Structure-activity Relationships of Flavonoids.

BACKGROUND: Flavonoids are a class of polyphenolic bioactive compounds obtained from plants, which have a wide range of chemical structures and properties. More than 9000 distinct flavonoid molecules have been identified and have been found to regulate numerous developmental processes and play key biological roles in living organisms. OBJECTIVE: This review aims to highlight the hepatoprotective potentiality of flavonoids and corelate their pharmacological activity with their chemical structure. METHODS: With the advancement in the field of research related to phytochemicals, it is evident that flavonoids have versatile health benefits, viz., antioxidant property, free radical scavenging capacity, anticancer activity. The basic structures are C6-C3-C6 rings with various substitution patterns, resulting in a succession of subclass compounds, and the relationships between chemical structures and bioactivity have previously been investigated. RESULTS: The hepatoprotective effects of bioactive flavonoids derived from plants have been widely linked to their antioxidant activity, antiinflammatory activity, effects on Sterol Regulatory Element- binding Proteins (SREBP), Peroxisome Proliferator-activated Receptor gamma (PPARγ) receptors, and inflammatory mediator cytokines according to numerous studies. The C2-C3 double bond at the A ring, as well as the hydroxyl groups of C3'or C4', and the carbonyl group at position C4, have been shown to augment their hepatoprotective activities; however, hydroxymethylation at C3' and C4' has been found to diminish the hepatoprotective activity. CONCLUSION: The impact of flavonoid moieties and the structure-activity relationship of flavonoids related to combating various hepatic disorders have been vividly discussed in this review paper.

Insight into the Various Approaches for the Enhancement of Bioavailability and Pharmacological Potency of Terpenoids: A Review.

Terpenoids are naturally occurring secondary metabolites that consist of isoprene units (i.e., 2-methyl-1,3-butadiene). Terpenoids became recognized because of their diverse pharmacological benefits, such as anti-cancer, anti-inflammatory, antioxidant, analgesic, antibacterial, antifungal, hepatoprotective, antiviral, and antiparasitic activities. But most of these compounds have limited lipophilicity, dissolution rate, aqueous solubility, and drug permeability, so they are not used effectively. The low bioavailability significantly interferes with the performance of terpenoids to cure diseases, and the absorption process of terpenoids also becomes disrupted; therefore, their bioavailability in the blood becomes insufficient to achieve optimal treatment activity. Thus, to overcome this limitation, some strategies are used, such as nanotechnology (nanoparticles, carrier complexation), cocrystal, and glycosylation. Thus, this review summarizes the chemistry of terpenoids, factors that limit the bioavailability of terpenoids, and strategies employed to date with their design principles and outcomes possibly increasing their bioactivity.

Pyridine Moiety: An Insight into Recent Advances in the Treatment of Cancer.

The incidence of cancer is increasing worldwide, affecting a vast majority of the human population, therefore, new different anticancer agents are being developed now and their safety still needs to be evaluated. Among them, pyridine based drugs are contributing a lot, as they are one of the imperative pharmacophores occurring synthetically as well as naturally in heterocyclic compounds, having a wide-range of therapeutic applications in the area of drug discovery that offers many chances for further improvement in antitumor agents via acting onto numerous receptors of extreme prominence. Many pyridine derivatives are reported to inhibit enzymes, receptors and many other targets for controlling and curing the global health issue of cancer. Nowadays in combination with other moieties, researchers are focusing on the development of pyridine-based new derivatives for cancer treatment. Therefore, this review sheds light on the recent therapeutic expansion of pyridine together with its molecular docking, structure-activity-relationship, availability in the market, a summary of recently patented and published research works that shall jointly help the scientists to produce effective drugs with the desired pharmacological activity.

An insight into primary biliary cholangitis and its recent advances in treatment: semi-synthetic analogs to combat ursodeoxycholic-acid resistance.

INTRODUCTION: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease which on progression causes cirrhosis; various studies also suggested that several diseases can co-exist in patients. In existing depiction of disease PBC, apart from entire use of ursodeoxycholic acid (UDCA), several patients need to step forward to liver-transplantation or death due to resistance or non-responder with UDCA monotherapy. AREAS COVERED: To overcome this non-respondent treatment, novel bile acid semi-synthetic analogs have been identified which shows their potency against for farnesoid X receptor and transmembrane G protein-coupled receptor-5 which are identified as target for many developing analogs which have desirable pharmacokinetic profiles. EXPERT OPINION: A range of studies suggests that adding semisynthetic analogs in therapeutic regime improves liver biochemistries in patients with suboptimal response to UDCA. Thus, the aspire of this review is to abridge and compare therapeutic value and current markets affirm of various bile acids semi-synthetic analogs which certainly are having promising effects in PBC monotherapy or in pooled treatment with UDCA for PBC.