Natural compounds such as polyphenols play several positive roles in maintaining the oxidative and inflammatory capacity of cells, which leads to their potential use as anticancer therapeutics. There is promising evidence for the in vitro and in vivo anticancer activity of many polyphenols, including resveratrol and quercetin, specifically in the treatment of colorectal cancer (CRC). There is a clear association between resveratrol and quercetin in interfering with the mechanistic pathways involved in CRC, such as Wnt, P13K/AKT, caspase-3, MAPK, NF-κB, etc. These molecular pathways establish the role of resveratrol and quercetin in controlling cancer cell growth, inducing apoptosis, and inhibiting metastasis. The major bottleneck in the progression of the use of resveratrol and quercetin as anticancer therapeutics is their reduced bioavailability in vivo because of their rapid metabolism in humans. Recent advancements in various nanotechnological formulations are promising for overcoming these bioavailability issues. Various nanoformulations of resveratrol and quercetin have shown an optimistic impact on reducing the solubility and improving the stability of resveratrol and quercetin in vivo. A combinatorial approach using nanoformulations of resveratrol with quercetin could potentially increase the impact of resveratrol in controlling CRC cell proliferation. This review discusses the mechanism of resveratrol and quercetin, the two bioactive polyphenolics, in colon cancer, with an emphasis on various types of nanoformulations of the two molecules targeting colon cancer. It also explores the synergistic effect of combining resveratrol and quercetin in various nanoformulations, targeting colon cancer. This research delves into the enhanced pharmacokinetics and potential chemotherapeutic benefits of these bioactive polyphenolics when used together in innovative ways.

A drug design strategy with reduced side effects and economic feasibility is desirable for fatal diseases. Increasing the bioavailability of a drug using a bioenhancer is a smart strategy. Herbal/natural bioenhancers with no probable side effects are an ideal choice to enhance the pharmacokinetics of a therapeutic drug synergistically. The mechanism of bioenhancers relies on the retention of the drug molecule in the cell without causing any changes in the metabolic activity. Most of the herbal bioenhancers achieve this feat by inhibiting metabolic enzymes such as cytochrome P450 and Uridine 5′-diphospho-glucuronosyltransferase. The efflux pump p-glycoprotein, responsible for removal of xenobiotics, is also inhibited by herbal/natural bioenhancers. The increased bioavailability because of the higher C_max and t_max of chemotherapeutics or anti-infectious agents such as rifampicin can result in a lower drug dosage regimen. The reduction in drug dosage is directly linked to fewer side effects and economic viability. Further, there is a significant effort in clinical trials to incorporate bioenhancers in drug regimens for cancer. The role of herbal/natural bioenhancers and their potential to augment the bioavailability of therapeutics used in cancer and infectious diseases, with a focus on the mechanisms of action, clinical studies and patents, have been summarized in this review article.

The significance of Autoimmune Disorders (Ads) is underscored by their chronic nature, high maintenance costs, and complexity affecting numerous organs and tissues. A more comprehensive approach to treating Ads is required across patient populations. A revo-lutionary area for obtaining an integrated therapeutic option is natural phytoconstituents. Di-verse biomolecules with promising properties can be found in abundance in the marine envi-ronment. Many substances have been identified from sponges, bacteria, fungi, cyanobacteria, and algae that have been shown to have immunomodulatory activities and may be used as possible treatments for Ads. Marine-derived bioactive substances have been demonstrated to affect immunological responses and to be essential in immunotherapies. The amount of in-formation about the specific effects of substances obtained from marine sources utilized as di-etary supplements or for treating immune-related diseases is growing. This paper discusses many sources of potential marine metabolic chemicals, such as maritime flora and fauna. Nu-merous marine phytoconstituents have recently been isolated, described, and identified, and they are currently undergoing human usage studies. We have attempted to consolidate infor-mation concerning phytoconstituents from marine sources with anti-inflammatory and im-munomodulatory properties in this review, and we have briefly explored their methods of ac-tion. In order to provide a baseline of knowledge for promoting marine flora-based phytocon-stituents in the current context of increasing Ads incidence, deprived of the more affordable, safe, and effective medications to combat the terrible human disease, this paper reviews the works thus far conducted on this aspect.

Mutations and their manifestations in the form of various diseases and disorders result in cancer which is a major cause of human death worldwide. A considerable amount of information is available at the cellular, molecular and genetic levels regarding the occurrence and spread of precarious cancer; yet, there is no cure. The traditional methods of treatment such as chemotherapy, radiotherapy and surgical intervention have shown to be moderately effective and to keep some types of cancer under control, but each modality has its own advantages and disadvantages. In recent years, more advanced methods such as targeted therapies, immunotherapy, and precision medicine are shown to be promising, and these fields continue to expand rapidly along with the conventional methods. This review focuses on the reports of advanced methods of treatment from a scientific standpoint to recognize many new and modern approaches. Selective targeting of the tumour cells by nanoparticle-based novel drug delivery approaches includes the latest innovations in their preparation strategies and applications. The concept of precision medicine and its impact on treatment are highlighted here with the hope of individualised therapy with minimum side effects as a part of ever-expanding treatment strategies. Additional challenges related to cancer treatment like multi-drug resistance and toxicity are also deliberated in brief. Based on the available reports and scientific evidence, better targeted approaches with better quality clinical outcomes and more precise drug delivery to fit individual treatment needs are anticipated in the near future to control this deadly disease.

DNA damage repair is a hallmark of any cancer growth, eventually leading to drug resistance and death. The poly ADP-ribose polymerase (PARP) enzyme is vital in repairing damaged DNA in normal and cancer cells with mutated DNA damage response (DDR) genes. Inhibitors of the PARP enzyme aid in chemotherapy, as shown by drug combinations such as Olaparib and Irinotecan in breast cancer treatment. However, the effect of Olaparib in colon cancer has not been studied extensively. Synthetic drugs have a significant limitation in cancer treatment due to drug resistance, leading to colon cancer relapse. Bioavailability of Olaparib and other PARP inhibitors is limited due to their hydrophobicity, which poses a significant challenge. These limitations and challenges can be addressed by encapsulating Olaparib in nanoparticles that could possibly increase the bioavailability of the drug at the site of action. New age nanoparticles, such as hybrid nanoparticles, provide superior quality in terms of design and circulatory time of the drug in the plasma. The side effects of Olaparib as a chemotherapeutic pave the way for exploring phytochemicals that may have similar effects. The combined impact of Olaparib and phytochemicals such as genistein, resveratrol and others in nano-encapsulated form can be explored in the treatment of colon cancer.

Background/Objectives: Poor oral bioavailability and limited intestinal permeation restrict the clinical translation of phytochemicals for colorectal cancer (CRC) therapy. The present preliminary study explored the development of a nanoparticle-based combinatorial formulation of resveratrol (Resv), acetyl-11-keto-β-boswellic acid (AKBA), and quercetin (Quer), to improve intestinal permeation and anti-cancer efficacy. Methods: A triple phytochemical nano formulation (designated as 3X) was developed and evaluated for morphology, particle size, zeta potential, encapsulation efficiency, and in vitro pharmaceutical characteristics. Safety was evaluated using in vitro cytotoxicity assays, while anticancer efficacy and apoptotic potential were preliminarily evaluated in Caco-2 CRC cell lines. Gene expression analysis was performed to examine the modulation of inflammation and cancer-related markers. Results: The 3X formulation exhibited a particle size of 198.5 nm with a polydispersity index of 0.492 and a zeta potential of −32.7, indicating good nanoscale stability. The encapsulation efficiencies were 90% for AKBA, 80% for Resv, and 75% for Quer. In vitro permeation studies demonstrated a controlled release mechanism. The formulation showed minimal hemolysis (3%) and had acceptable in vitro safety. The IC50 of the formulation was found to be 365 µg in the cytotoxicity assay. Treatment with the 3X nanoformulation significantly modulated anti-inflammatory and cancer-related gene expression in Caco2 cells, evidenced by downregulation of TGFβ (Transforming Growth Factor-beta) and COX-2 (cyclooxygenase-2), and upregulation of TNFα (Tumor necrosis factor-alpha) and nitric oxide (NO) and reduced IL-1β (Interleukins-1 beta) expression compared with control cells. Conclusions: The findings demonstrate that the developed 3X nano formulation exhibits favorable permeation characteristics and exerts anticancer activity against CRC. Based on preliminary findings, the formulation represents a promising phytochemical-based combination strategy for CRC, warranting further in vivo studies to validate its efficacy and elucidate the underlying molecular mechanisms.