Role of Quercetin in DNA Repair: Possible Target to Combat Drug Resistance in Diabetes.

Diabetes Mellitus (DM) is referred to as hyperglycemia in either fasting or postprandial phases. Oxidative stress, which is defined by an excessive amount of reactive oxygen species (ROS) production, increased exposure to external stress, and an excessive amount of the cellular defense system against them, results in cellular damage. Increased DNA damage is one of the main causes of genomic instability, and genetic changes are an underlying factor in the emergence of cancer. Through covalent connections with DNA and proteins, quercetin has been demonstrated to offer protection against the creation of oxidative DNA damage. It has been found that quercetin shields DNA from possible oxidative stress-related harm by reducing the production of ROS. Therefore, Quercetin helps to lessen DNA damage and improve the ability of DNA repair mechanisms. This review mainly focuses on the role of quercetin in repairing DNA damage and compensating for drug resistance in diabetic patients. Data on the target topic was obtained from major scientific databases, including SpringerLink, Web of Science, Google Scholar, Medline Plus, PubMed, Science Direct, and Elsevier. In preclinical studies, quercetin guards against DNA deterioration by regulating the degree of lipid peroxidation and enhancing the antioxidant defense system. By reactivating antioxidant enzymes, decreasing ROS levels, and decreasing the levels of 8-hydroxydeoxyguanosine, Quercetin protects DNA from oxidative damage. In clinical studies, it was found that quercetin supplementation was related to increased antioxidant capacity and decreased risk of type 2 diabetes mellitus in the experimental group as compared to the placebo group. It is concluded that quercetin has a significant role in DNA repair in order to overcome drug resistance in diabetes.

Physicochemical properties, pharmacokinetic studies, DFT approach, and antioxidant activity of nitro and chloro indolinone derivatives.

The process of developing of new drugs is greatly hampered by their inadequate physicochemical, pharmacokinetic, and intrinsic characteristics. In this regard, the selected chloro indolinone, (Z)-6-chloro-3-(2-chlorobenzylidene)indolin-2-one (C1), and nitro indolinone, (Z)-6-chloro-3-(2-nitrobenzylidene)indolin-2-one (C2), were subjected to SwissADME and density function theory (DFT) analysis. For compounds C1 and C2, the BOILED-Egg pharmacokinetic model predicted intestinal absorption, blood-brain barrier (BBB) penetration, and p-glycoprotein interaction. According to the physicochemical analysis, C1 has exceptional drug-like characteristics suitable for oral absorption. Despite only being substrates for some of the major CYP 450 isoforms, compounds C1 and C2 were anticipated to have strong plasma protein binding and efficient distribution and block these isoforms. The DFT study using the B3LYP/6-311G(d,p) approach with implicit water effects was performed to assess the structural features, electronic properties, and global reactivity parameters (GRP) of C1 and C2. The DFT results provided further support for other studies, implying that C2 is more water-soluble than C1 and that both compounds can form hydrogen bonds and (weak) dispersion interactions with other molecules, such as solvents and biomolecules. Furthermore, the GRP study suggested that C1 should be more stable and less reactive than C2. A concentration-dependent 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity was shown by both C1 and C2. In brief, this finding has provided a strong foundation to explore further the therapeutic potential of these molecules against a variety of human disorders.

Synthesis, in-vitro inhibition of cyclooxygenases and in silico studies of new isoxazole derivatives.

Isoxazole belongs to the class of five-membered heterocyclic compounds. The process of developing new drugs has significantly gained attention due to inadequate pharmacokinetic and safety attributes of the available drugs. This study aimed to design a new diverse array of ten novel isoxazole derivatives via Claisen Schmidt condensation reaction. In vitro COX-1/2 anti-inflammatory assay, in silico molecular docking of potent compounds, Molecular docking simulation, and SwissADME pharmacokinetic profile were investigated in this research. The in vitro COX-1 and COX-2 enzyme inhibitory assay showed that almost all the tested compounds exhibited anti-inflammatory effects whereas C6, C5, and C3 were found to be the most potent COX-2 enzyme inhibitors among the tested compounds and are good candidates for selective COX-2 inhibitors. In silico molecular docking studies coupled with molecular dynamic simulation has been done to rationalize the time-evolved mode of interaction of selected inhibitor inside the active pockets of target COX-2. The binding orientations and binding energy results also showed the selectivity of compounds towards COX-2. Physicochemical properties, pharmacokinetic profile, lipophilicity, water solubility, drug metabolism, drug-likeness properties, and medicinal chemistry of the synthesized isoxazole derivatives were assessed. The SwissADME (absorption, distribution, metabolism, and excretion) database was used to assess the physicochemical properties and drug-likeness properties of the synthesized isoxazole derivatives. All the compounds were shown high GI absorption except Compound 7 (C7). Compound 1 (C1) and Compound 2 (C2) were found to cross the blood-brain barrier (BBB). Lipinski's rule of five is not violated by any of the ten synthesized isoxazole derivatives. It was predicted with the SwissADME database that C2, C5, C6, C7, and C8 are potent inhibitors of cytochrome (CYP) subtype CYP-2C19. A subtype of CYP-2C9 was inhibited by C4 and C7. The medicinal chemistry of all the compounds C1-C10 showed no PAIN (Pan assay interference compounds) alerts. The improved gastrointestinal (GI) absorption and BBB permeability of C1 and C2 can provide a future prospective for new researchers in the medicinal field to investigate the compounds for the management of chronic diseases. The synthesized isoxazole compounds showed excellent in vitro COX-1/2 enzymes anti-inflammatory investigations, in silico studies, good physicochemical properties, and improved pharmacokinetic profile which will be further investigated via in vivo anti-inflammatory activities. Moreover, to further support our findings of the computational research and in vitro studies, an in-vivo pharmacokinetic profile is suggested in the future.

How gallic acid regulates molecular signaling: role in cancer drug resistance.

Cancer is one of the deadliest and most heterogeneous diseases. Cancers often develop drug resistance, which can lead to treatment failure or recurrence. Accordingly, anticancer compounds are essential for chemotherapy-resistant cancer cells. Phenolic compounds are of interest in the development of cancer drugs due to their medicinal properties and ability to target different molecular pathways. Gallic acid (GA), as one of the main components of phenol, which is abundantly present in plant compounds such as walnut, sumac, grapes, tea leaves, oak bark, and other plant compounds, has antitumor properties. GA can prevent cancer progression, cell invasion, and metastasis by targeting molecular pathways and is an effective complement to chemotherapy drugs and combating multidrug resistance (MDR). In this review, we discuss various mechanisms related to cancer, the therapeutic potential of GA, the antitumor properties of GA in various cancers, and the targeted delivery of GA with nanocarriers.

Marine Cyanobacterial Peptides in Neuroblastoma: Search for Better Therapeutic Options.

Neuroblastoma is the most prevalent extracranial solid tumor in pediatric patients, originating from sympathetic nervous system cells. Metastasis can be observed in approximately 70% of individuals after diagnosis, and the prognosis is poor. The current care methods used, which include surgical removal as well as radio and chemotherapy, are largely unsuccessful, with high mortality and relapse rates. Therefore, attempts have been made to incorporate natural compounds as new alternative treatments. Marine cyanobacteria are a key source of physiologically active metabolites, which have recently received attention owing to their anticancer potential. This review addresses cyanobacterial peptides' anticancer efficacy against neuroblastoma. Numerous prospective studies have been carried out with marine peptides for pharmaceutical development including in research for anticancer potential. Marine peptides possess several advantages over proteins or antibodies, including small size, simple manufacturing, cell membrane crossing capabilities, minimal drug-drug interactions, minimal changes in blood-brain barrier (BBB) integrity, selective targeting, chemical and biological diversities, and effects on liver and kidney functions. We discussed the significance of cyanobacterial peptides in generating cytotoxic effects and their potential to prevent cancer cell proliferation via apoptosis, the activation of caspases, cell cycle arrest, sodium channel blocking, autophagy, and anti-metastasis behavior.

Therapeutic potential of marine peptides in malignant melanoma.

Malignant melanoma is the most dangerous type of skin cancer. It is becoming more common globally and is increasingly resistant to treatment options. Despite extensive research into its pathophysiology, there are still no proven cures for metastatic melanoma. Unfortunately, current treatments are frequently ineffective and costly, and have several adverse effects. Natural substances have been extensively researched for their anti-MM capabilities. Chemoprevention and adjuvant therapy with natural products is an emerging strategy to prevent, cure or treat melanoma. Numerous prospective drugs are found in aquatic species, providing a plentiful supply of lead cytotoxic chemicals for cancer treatment. Anticancer peptides are less harmful to healthy cells and cure cancer through several different methods, such as altered cell viability, apoptosis, angiogenesis/metastasis suppression, microtubule balance disturbances and targeting lipid composition of the cancer cell membrane. This review addresses marine peptides as effective and safe treatments for MM and details their molecular mechanisms of action.

Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches.

Diabetes mellitus (DM) is counted among one of the leading challenges in the recent era, and it is a life-threatening disorder. Compound 4-hydroxy 3-methoxy phenylacetone (compound 1) was previously isolated from Polygonum aviculare. This compound was reacted with N-benzylmaleimide to synthesize the targeted compound 3. The purpose of this research is to exhibit our developed compound 3's ability to concurrently inhibit many targets that are responsible for hyperglycemia. Compound 3 was capable of inhibiting α-amylase, α-glucosidase, and protein tyrosine phosphatase 1 B. Even so, outstanding in vitro inhibition was shown by the compound against dipeptidyl peptidase-4 (DPP-4) with an IC50 value of 0.07 µM. Additionally, by using DPPH in the antioxidant activity, it exhibited good antioxidant potential. Similarly, in the in vivo activity, the experimental mice proved to be safe by treatment with compound 3. After 21 days of examination, the compound 3 activity pattern was found to be effective in experimental mice. Compound 3 decreased the excess peak of total triglycerides, total cholesterol, AST, ALT, ALP, LDL, BUN, and creatinine in the STZ-induced diabetic mice. Likewise, the histopathology of the kidneys, liver, and pancreas of the treated animals was also evaluated. Overall, the succinimde moiety, such as compound 3, can affect several targets simultaneously, and, finally, we were successful in synthesizing a multi-targeted preclinical therapy.

Resveratrol regulates inflammation and improves oxidative stress via Nrf2 signaling pathway: Therapeutic and biotechnological prospects.

Usually, in aerobic metabolism, natural materials including nucleic acids, proteins, and lipids can experience auxiliary injury by oxidative responses. This damage produced by reactive oxygen/nitrogen species has been identified as "oxidative stress." As a natural polyphenol got from red wine and peanuts, resveratrol is one of the most eminent anti-aging mixtures. Based on many studies', resveratrol hinders destructive effects of inflammatory causes and reactive oxygen radicals in several tissues. The nuclear erythroid 2-related factor 2 is a factor related to transcription with anti-inflammatory, antioxidant possessions which is complicated by enzyme biotransformation and biosynthesis of lipids and carbohydrates. This review provides current understanding and information about the character of resveratrol against oxidative stress and regulation of inflammation via Nrf2 signaling pathway.

Natural products targeting the ATR-CHK1 signaling pathway in cancer therapy.

Cancer is one of the most severe medical conditions in the world, causing millions of deaths each year. Chemotherapy and radiotherapy are critical for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer requires novel efficacious treatment modalities. Natural remedies offer feasible alternative options against malignancy in contrast to available synthetic medication. Selective killing of cancer cells is privileged mainstream in cancer treatment, and targeted therapy represents the new tool with the potential to pursue this aim. The discovery of innovative therapies targeting essential components of DNA damage signaling and repair pathways such as ataxia telangiectasia mutated and Rad3 related Checkpoint kinase 1 (ATR-CHK1)has offered a possibility of significant therapeutic improvement in oncology. The activation and inhibition of this pathway account for chemopreventive and chemotherapeutic activity, respectively. Targeting this pathway can also aid to overcome the resistance of conventional chemo- or radiotherapy. This review enlightens the anticancer role of natural products by ATR-CHK1 activation and inhibition. Additionally, these compounds have been shown to have chemotherapeutic synergistic potential when used in combination with other anticancer drugs. Ideally, this review will trigger interest in natural products targeting ATR-CHK1 and their potential efficacy and safety as cancer lessening agents.

Therapeutic Potential of Marine Peptides in Prostate Cancer: Mechanistic Insights.

Prostate cancer (PCa) is the leading cause of cancer death in men, and its treatment is commonly associated with severe adverse effects. Thus, new treatment modalities are required. In this context, natural compounds have been widely explored for their anti-PCa properties. Aquatic organisms contain numerous potential medications. Anticancer peptides are less toxic to normal cells and provide an efficacious treatment approach via multiple mechanisms, including altered cell viability, apoptosis, cell migration/invasion, suppression of angiogenesis and microtubule balance disturbances. This review sheds light on marine peptides as efficacious and safe therapeutic agents for PCa.

Flavonoids Targeting the mTOR Signaling Cascades in Cancer: A Potential Crosstalk in Anti-Breast Cancer Therapy.

Cancer is one of the leading causes of death worldwide. Breast cancer is the second leading cause of death in women, with triple-negative breast cancer being the most lethal and aggressive form. Conventional therapies, such as radiation, surgery, hormonal, immune, gene, and chemotherapy, are widely used, but their therapeutic efficacy is limited due to adverse side effects, toxicities, resistance, recurrence, and therapeutic failure. Many molecules have been identified and investigated as potential therapeutic agents for breast cancer, with a focus on various signaling pathways. Flavonoids are a versatile class of phytochemicals that have been used in cancer treatment to overcome issues with traditional therapies. Cell proliferation, growth, apoptosis, autophagy, and survival are all controlled by mammalian target of rapamycin (mTOR) signaling. Flavonoids target mTOR signaling in breast cancer, and when this signaling pathway is regulated or deregulated, various signaling pathways provide potential therapeutic means. The role of various flavonoids as phytochemicals in targeting mTOR signaling pathways in breast cancer is highlighted in this review.

How Curcumin Targets Inflammatory Mediators in Diabetes: Therapeutic Insights and Possible Solutions.

Diabetes mellitus is a multifactorial chronic metabolic disorder, characterized by altered metabolism of macro-nutrients, such as fats, proteins, and carbohydrates. Diabetic retinopathy, diabetic cardiomyopathy, diabetic encephalopathy, diabetic periodontitis, and diabetic nephropathy are the prominent complications of diabetes. Inflammatory mediators are primarily responsible for these complications. Curcumin, a polyphenol derived from turmeric, is well known for its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. The regulation of several signaling pathways effectively targets inflammatory mediators in diabetes. Curcumin's anti-inflammatory and anti-oxidative activities against a wide range of molecular targets have been shown to have therapeutic potential for a variety of chronic inflammatory disorders, including diabetes. Curcumin's biological examination has shown that it is a powerful anti-oxidant that stops cells from growing by releasing active free thiol groups at the target location. Curcumin is a powerful anti-inflammatory agent that targets inflammatory mediators in diabetes, and its resistant form leads to better therapeutic outcomes in diabetes complications. Moreover, Curcumin is an anti-oxidant and NF-B inhibitor that may be useful in treating diabetes. Curcumin has been shown to inhibit diabetes-related enzymes, such as a-glucosidase, aldose reductase and aldose reductase inhibitors. Through its anti-oxidant and anti-inflammatory effects, and its suppression of vascular endothelial development and nuclear transcription factors, curcumin has the ability to prevent, or reduce, the course of diabetic retinopathy. Curcumin improves insulin sensitivity by suppressing phosphorylation of ERK/JNK in HG-induced insulin-resistant cells and strengthening the PI3K-AKT-GSK3B signaling pathway. In the present article, we aimed to discuss the anti-inflammatory mechanisms of curcumin in diabetes regulated by various molecular signaling pathways.

Neuroblastoma: Essential genetic pathways and current therapeutic options.

Neuroblastoma is a very diverse pediatric tumor that starts from the neural crest, and it is responsible over more than 15% of all juvenile cancer deaths. Clinical signs and symptoms are highly dependent on tumor origin and spread. Bone, lymph nodes, liver, intracranial and orbital tissues, lungs, and the central nervous system are frequently involved in metastatic neuroblastoma. Neuroblastoma enhances with contrast in Computed Tomography (CT) scans as a solid heterogeneous mass which might invade to adjacent ipsilateral or contralateral lymph nodes, tissues, and vessels. Whereas the Magnetic Resonance Imaging (MRI) acquires an acceptable diagnostic accuracy for detection of spinal cord and musculoskeletal metastases. Lorlatinib, a novel ALK inhibitor designed to overcome this resistance, is currently being tested in the New Approaches to Neuroblastoma Therapy (NANT) consortium. Aurora kinase inhibitors have been reported to disrupt MYCN, which is particularly attractive considering the lack of direct inhibitors targeting this driver in neuroblastoma. Sorafenib, a RAF kinase inhibitor, and newer PI3K inhibitors are being tested in children with neuroblastoma in an attempt to block the RAS pathway. Despite various therapies including chemotherapy, radiotherapy, immunotherapy and autologous stem cell transplantation in different neuroblastoma risk groups, most patients undergo surgical removal of the tumoral mass. This review is aimed to summarize the updated knowledge about the neuroblastoma, pathogenesis, it's essential genetic pathways and the current available therapeutic options for neuroblastoma.

The Role of NRF2/KEAP1 Pathway in Glioblastoma: Pharmacological Implications.

Glioblastoma multiforme (GBM) grade IV glioma is the most frequent and deadly intracranial cancer. This tumor is determined by unrestrained progression, uncontroled angiogenesis, high infiltration and weak response to treatment, which is chiefly because of abnormal signaling pathways in the tumor. A member related to the Cap 'n' collar family of keypart-leucine zipper transcription agents-the transcription factor NF-E2-related factor 2 (Nrf2)-regulates adaptive protection answers by organized upregulation of many genes that produce the cytoprotective factors. In reply to cellular pressures types such as stresses, Nrf2 escapes Kelch-like ECH-related protein 1 (Keap1)-facilitated suppression, moves from the cytoplasm towards the nucleus and performs upregulation of gene expression of antioxidant responsive element (ARE). Nrf2 function is related tocontrolling many types of diseases in the human specially GBM tumor.Thus, we will review the epigeneticalregulatory actions on the Nrf2/Keap1 signaling pathway and potential therapeutic options in GBM by aiming the stimulation of Nrf2.

The Regulation of Endoplasmic Reticulum Stress in Cancer: Special Focuses on Luteolin Patents.

Cancer is a major health problem across the globe, and is expeditiously growing at a faster rate worldwide. The endoplasmic reticulum (ER) is a membranous cell organelle having inextricable links in cellular homeostasis. Altering ER homeostasis initiates various signaling events known as the unfolded protein response (UPR). The basic purpose of the UPR is to reinstate the homeostasis; however, a continuous UPR can stimulate pathways of cell death, such as apoptosis. As a result, there is great perturbation to target particular signaling pathways of ER stress. Flavonoids have gained significant interest as a potential anticancer agent because of their considerable role in causing cytotoxicity of the cancerous cells. Luteolin, a flavonoid isolated from natural products, is a promising phytochemical used in the treatment of cancer. The current study is designed to review the different endoplasmic reticulum stress pathways involved in the cancer, mechanistic insights of luteolin as an anticancer agent in modulating ER stress, and the available luteolin patent formulations were also highlighted. The patents were selected on the basis of pre-clinical and/or clinical trials, and established antitumor effects using patent databases of FPO IP and Espacenet. The patented formulation of luteolin studied so far has shown promising anticancer potential against different cancer cell lines. However, further research is still required to determine the molecular targets of such bioactive molecules so that they can be used as anticancer drugs.

Antimicrobial Potential of Curcumin: Therapeutic Potential and Challenges to Clinical Applications.

Curcumin is a bioactive compound that is extracted from Curcuma longa and that is known for its antimicrobial properties. Curcuminoids are the main constituents of curcumin that exhibit antioxidant properties. It has a broad spectrum of antibacterial actions against a wide range of bacteria, even those resistant to antibiotics. Curcumin has been shown to be effective against the microorganisms that are responsible for surgical infections and implant-related bone infections, primarily Staphylococcus aureus and Escherichia coli. The efficacy of curcumin against Helicobacter pylori and Mycobacterium tuberculosis, alone or in combination with other classic antibiotics, is one of its most promising antibacterial effects. Curcumin is known to have antifungal action against numerous fungi that are responsible for a variety of infections, including dermatophytosis. Candidemia and candidiasis caused by Candida species have also been reported to be treated using curcumin. Life-threatening diseases and infections caused by viruses can be counteracted by curcumin, recognizing its antiviral potential. In combination therapy with other phytochemicals, curcumin shows synergistic effects, and this approach appears to be suitable for the eradication of antibiotic-resistant microbes and promising for achieving co-loaded antimicrobial pro-regenerative coatings for orthopedic implant biomaterials. Poor water solubility, low bioavailability, and rapid degradation are the main disadvantages of curcumin. The use of nanotechnologies for the delivery of curcumin could increase the prospects for its clinical application, mainly in orthopedics and other surgical scenarios. Curcumin-loaded nanoparticles revealed antimicrobial properties against S. aureus in periprosthetic joint infections.

Regulation of endoplasmic reticulum stress by hesperetin: Focus on antitumor and cytoprotective effects.

BACKGROUND: Cancer is still an all-times issue due to a large and even increasing number of deaths. Impaired genes regulating cell proliferation and apoptosis are targets for the development of novel cancer treatments. HYPOTHESIS: Increased transcription of NADPH oxidase activator (NOXA), Bcl2-like11 (BIM), BH3-only proteins and p53 unregulated apoptosis modulator (PUMA) is caused by the imbalance between pro- and anti-apoptotic Bcl-2 proteins due to endoplasmic reticulum (ER) stress. The membranous network of ER is present in all eukaryotic cells. ER stress facilitates the interaction between Bax and PUMA, triggering the release of cytochrome C. As a main intracellular organelle, ER is responsible for translocation as well as post-translation modification and protein folding. RESULTS: Hesperetin is a cytoprotective flavonone, which acts against ER stress and protects from cell damage induced by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Hesperetin inhibits lipid peroxidation induced by Fe2+ and l-ascorbic acid in rat brain homogenates. CONCLUSION: This review deals with the anticancer effects of hesperetin regarding the regulation of ER stress as a principal mechanism in the pathogenesis of tumors.

Alkaloids and Colon Cancer: Molecular Mechanisms and Therapeutic Implications for Cell Cycle Arrest.

Cancer is the second most fatal disease worldwide, with colon cancer being the third most prevalent and fatal form of cancer in several Western countries. The risk of acquisition of resistance to chemotherapy remains a significant hurdle in the management of various types of cancer, especially colon cancer. Therefore, it is essential to develop alternative treatment modalities. Naturally occurring alkaloids have been shown to regulate various mechanistic pathways linked to cell proliferation, cell cycle, and metastasis. This review aims to shed light on the potential of alkaloids as anti-colon-cancer chemotherapy agents that can modulate or arrest the cell cycle. Preclinical investigated alkaloids have shown anti-colon cancer activities and inhibition of cancer cell proliferation via cell cycle arrest at different stages, suggesting that alkaloids may have the potential to act as anticancer molecules.

Nanoscale delivery of phytochemicals targeting CRISPR/Cas9 for cancer therapy.

BACKGROUND: With growing global prevalence, cancer is a major cause of disease-related deaths. The understanding of the fundamental tumor pathology has contributed to the development of agents targeting oncogenic signaling pathways. Although these agents have increased survival for defined cancers, the therapeutic choices are still limited due to the development of drug resistance. CRISPR/Cas9 is a powerful new technology in cancer therapy by facilitating the identification of novel treatment targets and development of cell-based treatment strategies. PURPOSE: We focused on applications of the CRISPR/Cas9 system in cancer therapy and discuss nanoscale delivery of cytotoxic phytochemical targeting the CRISPR/Cas9 system. RESULTS: Genome engineering has been significantly accelerated by the advancement of the CRISPR/Cas9 technique. Phytochemicals play a key role in treating cancer by targeting various mechanisms and pathways. CONCLUSIONS: The use of CRISPR/Cas9 for nanoscale delivery of phytochemicals opens new avenues in cancer therapy. One of the main obstacles in the clinical application of CRISPR/Cas9 is safe and efficient delivery. As viral delivery methods have certain drawbacks, there is an urgent need to develop non-viral delivery systems for therapeutic applications.

Multifaceted Pharmacological Potentials of Curcumin, Genistein, and Tanshinone IIA through Proteomic Approaches: An In-Depth Review.

Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future.