Capsaicin: A chili pepper bioactive phytocompound with a potential role in suppressing cancer development and progression.

Cancer profoundly influences morbidity and fatality rates worldwide. Patients often have dismal prognoses despite recent improvements in cancer therapy regimens. However, potent biomolecules derived from natural sources, including medicinal and dietary plants, contain biological and pharmacological properties to prevent and treat various human malignancies. Capsaicin is a bioactive phytocompound present in red hot chili peppers. Capsaicin has demonstrated many biological effects, including antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic capabilities. This review highlights the cellular and molecular pathways through which capsaicin exhibits antineoplastic activities. Our work also depicts the synergistic anticancer properties of capsaicin in conjunction with other natural bioactive components and approved anticancer drugs. Capsaicin inhibits proliferation in various cancerous cells, and its antineoplastic actions in numerous in vitro and in vivo carcinoma models impact oncogenesis, tumor-promoting and suppressor genes, and associated signaling pathways. Capsaicin alone or combined with other phytocompounds or approved antineoplastic drugs triggers cell cycle progression arrest, generating reactive oxygen species and disrupting mitochondrial membrane integrity, ultimately stimulating caspases and promoting death. Furthermore, capsaicin alone or in combination can promote apoptosis in carcinoma cells by enhancing the p53 and c-Myc gene expressions. In conclusion, capsaicin alone or in combination can have enormous potential for cancer prevention and intervention, but further high-quality studies are needed to firmly establish the clinical efficacy of this phytocompound.

Garlic constituents for cancer prevention and therapy: From phytochemistry to novel formulations.

Garlic (Allium sativum L.) is one of the oldest plants cultivated for its dietary and medicinal values. This incredible plant is endowed with various pharmacological attributes, such as antimicrobial, antiarthritic, antithrombotic, antitumor, hypoglycemic, and hypolipidemic activities. Among the various beneficial pharmacological effects of garlic, the anticancer activity is presumably the most studied. The consumption of garlic provides strong protection against cancer risk. Taking into account the multi-targeted actions and absence of considerable toxicity, a few active metabolites of garlic are probably to play crucial roles in the killing of cancerous cells. Garlic contains several bioactive molecules with anticancer actions and these include diallyl trisulfide, allicin, diallyl disulfide, diallyl sulfide, and allyl mercaptan. The effects of various garlic-derived products, their phytoconstituents and nanoformulations have been evaluated against skin, prostate, ovarian, breast, gastric, colorectal, oral, liver, and pancreatic cancers. Garlic extract, its phytocompounds and their nanoformulations have been shown to inhibit the different stages of cancer, including initiation, promotion, and progression. Besides, these bioactive metabolites alter the peroxidation of lipid, activity of nitric oxide synthetase, nuclear factor-κB, epidermal growth factor receptor, and protein kinase C, cell cycle, and survival signaling. The current comprehensive review portrays the functions of garlic, its bioactive constituents and nanoformulations against several types of cancers and explores the possibility of developing these agents as anticancer pharmaceuticals.

Marine Cyanobacteria and Microalgae Metabolites-A Rich Source of Potential Anticancer Drugs.

Cancer is at present one of the utmost deadly diseases worldwide. Past efforts in cancer research have focused on natural medicinal products. Over the past decades, a great deal of initiatives was invested towards isolating and identifying new marine metabolites via pharmaceutical companies, and research institutions in general. Secondary marine metabolites are looked at as a favorable source of potentially new pharmaceutically active compounds, having a vast structural diversity and diverse biological activities; therefore, this is an astonishing source of potentially new anticancer therapy. This review contains an extensive critical discussion on the potential of marine microbial compounds and marine microalgae metabolites as anticancer drugs, highlighting their chemical structure and exploring the underlying mechanisms of action. Current limitation, challenges, and future research pathways were also presented.

Star anise (Illicium verum): Chemical compounds, antiviral properties, and clinical relevance.

Medicinal herbs are one of the imperative sources of drugs all over the world. Star anise (Illicium verum), an evergreen, medium-sized tree with star-shaped fruit, is an important herb with wide distribution throughout southwestern parts of the Asian continent. Besides its use as spice in culinary, star anise is one of the vital ingredients of the Chinese medicinal herbs and is widely known for its antiviral effects. It is also the source of the precursor molecule, shikimic acid, which is used in the manufacture of oseltamivir (Tamiflu®), an antiviral medication for influenza A and influenza B. Besides, several other molecules with numerous biological benefits including the antiviral effects have been reported from the same plant. Except the antiviral potential, star anise possesses a number of other potentials such as antioxidant, antimicrobial, antifungal, anthelmintic, insecticidal, secretolytic, antinociceptive, anti-inflammatory, gastroprotective, sedative properties, expectorant and spasmolytic, and estrogenic effects. This review aimed to integrate the information on the customary attributes of the plant star anise with a specific prominence on its antiviral properties and the phytochemical constituents along with its clinical aptness.

Formulation development and systematic optimization of stabilized ziprasidone hydrochloride capsules devoid of any food effect.

CONTEXT AND OBJECTIVE: The objective of the study was to develop a stable capsule formulation of ziprasidone hydrochloride which can be administered without regards to food intake. MATERIALS AND METHODS: The unstable anhydrous form of ziprasidone hydrochloride was stabilized employing hot-melt extrusion and further optimized by 32 central composite design. The formulation was optimized after establishing acceptable ranges for response variables like disintegration time, dissolution and impurity profile. A crossover fasted and fed in vivo study was conducted in human volunteers to assess the food-effect of optimized formulation vis-à-vis the marketed brand. RESULTS AND DISCUSSION: The optimized formulation met in-house specifications for various response variables. Further, high values of correlation coefficient vouch the adequate selection of experimental design and its high prognostic ability. In our study, no significant difference was observed between the Cmax and AUC values after administration of the optimized formulation in fasted and fed states. On the contrary, there was a statistically significant increase in the Cmax and AUC values after oral administration of Zeldox in fed state in comparison to fasted state. CONCLUSIONS: The present study describes the successful development of a stable formulation of 20 mg of ziprasidone devoid of any food-effects.

Managing Postharvest Losses of Vegetables and Fruits: A Methodological Review.

Vegetables and fruits are highly perishable agricultural commodities cultivated all over the world. However, inadequate handling practices have led to significant postharvest losses of these agricultural commodities, as well as the wastage of valuable resources, such as time and money. Hence, it can be observed that cultivators often experience significant financial setbacks as a result of inadequate comprehension regarding the nature and origins of these losses, insufficient preservation practices, and ineffective approaches to transportation and marketing. In addition, the utilization of suitable chemical agents during both the pre- and postharvest phases has the potential to prolong the shelf life of agricultural products. This preservation technique safeguards vegetables and fruits from pathogenic organisms and other forms of environmental harm, thereby enabling their availability for an extended duration. Therefore, this review proposes a methodology for managing fruits and vegetables postharvest to minimize losses and optimize returns.

Unraveling the Ties: Type 2 Diabetes and Parkinson's Disease - A Nano-Based Targeted Drug Delivery Approach.

The link between Type 2 Diabetes (T2DM) and Parkinson's Disease (PD) dates back to the early 1960s, and ongoing research is exploring this association. PD is linked to dysregulation of dopaminergic pathways, neuroinflammation, decreased PPAR-γ coactivator 1-α, increased phosphoprotein enriched in diabetes, and accelerated α-Syn amyloid fibril production caused by T2DM. This study aims to comprehensively evaluate the T2DM-PD association and risk factors for PD in T2DM individuals. The study reviews existing literature using reputable sources like Scopus, ScienceDirect, and PubMed, revealing a significant association between T2DM and worsened PD symptoms. Genetic profiles of T2DM-PD individuals show similarities, and potential risk factors include insulin-resistance and dysbiosis of the gut-brain microbiome. Anti-diabetic drugs exhibit neuroprotective effects in PD, and nanoscale delivery systems like exosomes, micelles, and liposomes show promise in enhancing drug efficacy by crossing the Blood-Brain Barrier (BBB). Brain targeting for PD uses exosomes, micelles, liposomes, dendrimers, solid lipid nanoparticles, nano-sized polymers, and niosomes to improve medication and gene therapy efficacy. Surface modification of nanocarriers with bioactive compounds (such as angiopep, lactoferrin, and OX26) enhances α-Syn conjugation and BBB permeability. Natural exosomes, though limited, hold potential for investigating DM-PD pathways in clinical research. The study delves into the underlying mechanisms of T2DM and PD and explores current therapeutic approaches in the field of nano-based targeted drug delivery. Emphasis is placed on resolved and ongoing issues in understanding and managing both conditions.

Litchi (Litchi chinensis Sonn.): A comprehensive and critical review on cancer prevention and intervention.

Litchi (Litchi chinensis Sonn.) is a tropical fruit with various health benefits. The objective of this study is to present a thorough analysis of the cancer preventive and anticancer therapeutic properties of litchi constituents and phytocompounds. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria were followed in this work. Various litchi extracts and constituents were studied for their anticancer effects. In vitro studies showed that litchi-derived components reduced cell proliferation, induced cytotoxicity, and promoted autophagy via increased cell cycle arrest and apoptosis. Based on in vivo studies, litchi flavonoids and other extracted constituents significantly reduced tumor size, number, volume, and metastasis. Major signaling pathways impacted by litchi constituents were shown to stimulate proapoptotic, antiproliferative, and antimetastatic activities. Despite promising antineoplastic activities, additional research, especially in vivo and clinical studies, is necessary before litchi-derived products and phytochemicals can be used for human cancer prevention and intervention.

Non-healing verrucous plaque over upper limb for 1 year in a tea garden worker.

A 55-year-old tea garden worker presented with a slowly growing verrucous plaque on the right arm. The diagnosis of chromomycosis was confirmed by the identification of brown sclerotic bodies in a skin biopsy.

Natural Polymeric Nanobiocomposites for Anti-Cancer Drug Delivery Therapeutics: A Recent Update.

Cancer is one of the most common lethal diseases and the leading cause of mortality worldwide. Effective cancer treatment is a global problem, and subsequent advancements in nanomedicine are useful as substitute management for anti-cancer agents. Nanotechnology, which is gaining popularity, enables fast-expanding delivery methods in science for curing diseases in a site-specific approach, utilizing natural bioactive substances because several studies have established that natural plant-based bioactive compounds can improve the effectiveness of chemotherapy. Bioactive, in combination with nanotechnology, is an exceptionally alluring and recent development in the fight against cancer. Along with their nutritional advantages, natural bioactive chemicals may be used as chemotherapeutic medications to manage cancer. Alginate, starch, xanthan gum, pectin, guar gum, hyaluronic acid, gelatin, albumin, collagen, cellulose, chitosan, and other biopolymers have been employed successfully in the delivery of medicinal products to particular sites. Due to their biodegradability, natural polymeric nanobiocomposites have garnered much interest in developing novel anti-cancer drug delivery methods. There are several techniques to create biopolymer-based nanoparticle systems. However, these systems must be created in an affordable and environmentally sustainable way to be more readily available, selective, and less hazardous to increase treatment effectiveness. Thus, an extensive comprehension of the various facets and recent developments in natural polymeric nanobiocomposites utilized to deliver anti-cancer drugs is imperative. The present article provides an overview of the latest research and developments in natural polymeric nanobiocomposites, particularly emphasizing their applications in the controlled and targeted delivery of anti-cancer drugs.

Phytochemicals for the prevention and treatment of pancreatic cancer: Current progress and future prospects.

Pancreatic cancer is the third leading cause of cancer-related deaths in the United States, owing to its aggressive nature and suboptimal treatment options, emphasizing the need for novel therapeutic approaches. Emerging studies have exhibited promising results regarding the therapeutic utility of plant-derived compounds (phytochemicals) in pancreatic cancer. The purpose of this review is to evaluate the potential of phytochemicals in the treatment and prevention of pancreatic cancer. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was applied to collect articles for this review. Scholarly databases, including PubMed, Scopus and ScienceDirect, were queried for relevant studies using the following keywords: phytochemicals, phenolics, terpenoids, alkaloids, sulfur-containing compounds, in vitro, in vivo, clinical studies, pancreatic cancer, tumour, treatment and prevention. Aggregate results pooled from qualified studies indicate phytochemicals can inhibit pancreatic cancer cell growth or decrease tumour size and volume in animal models. These effects have been attributed to various mechanisms, such as increasing proapoptotic factors, decreasing antiapoptotic factors, or inducing cell death and cell cycle arrest. Notable signalling pathways modulated by phytochemicals include the rat sarcoma/mitogen activated protein kinase, wingless-related integration site/ß-catenin and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signal transduction pathways. Clinically, phytochemicals have been found to increase survival while being well-tolerated and safe, though research is scarce. While these promising results have produced great interest in this field, further in-depth studies are required to characterize the anticancer activities of phytochemicals before they can be utilized to prevent or treat pancreatic cancer in clinical practice.

Nutraceuticals, a Bridge Between Past and Future: Focus on Mushrooms Biological Activities and Myco-Chemistry.

BACKGROUND: Mushrooms are consumed worldwide due to their high nutritional and nutraceutical values. In addition to the presence of various vitamins, low-fat, and proteins, they are also an important source of trace elements, dietary fibers, and bioactive compounds. Their potential therapeutic properties are due to their multiple biological effects, such as antimicrobial, antiviral, antioxidant, anticancer, immune-modulating, cardioprotective, and antidiabetic properties. The global market of mushroom farming is anticipated to witness remarkable progress for its potential application in health products, profitable production and a rising demand for the healthy foods across the globe. The Asia Pacific marketplace seems to represent the major market of mushrooms, due to the higher per capita consumption of culinary and medical purposes. OBJECTIVE: Mushrooms have generally low calories, low levels of cholesterol, fats, gluten and sodium. Several biological effects of mushroom are due to the presence of phenolic components, polysaccharides, terpenoids, terphenyl-related compounds, and many other lower molecular weight molecules. This review aims at describing the chemical characterization of several mushrooms species and their biological effects. CONCLUSION: The current review describes different secondary metabolites found in several mushrooms and mushrooms extracts, and the molecular mechanisms underlying the biological activities. Also the antimicrobial activities of mushrooms, mushrooms extracts and isolated compounds from mushrooms were described. The description of these activities, related to the presence of specific classes of secondary metabolites and isolated compounds, may lead to the identification of mycomplexes and mushrooms compounds that may be further studied for their potential application in nutraceutical products.

Phenolic Phytochemicals for Prevention and Treatment of Colorectal Cancer: A Critical Evaluation of In Vivo Studies.

Colorectal cancer (CRC) is the third most diagnosed and second leading cause of cancer-related death worldwide. Limitations with existing treatment regimens have demanded the search for better treatment options. Different phytochemicals with promising anti-CRC activities have been reported, with the molecular mechanism of actions still emerging. This review aims to summarize recent progress on the study of natural phenolic compounds in ameliorating CRC using in vivo models. This review followed the guidelines of the Preferred Reporting Items for Systematic Reporting and Meta-Analysis. Information on the relevant topic was gathered by searching the PubMed, Scopus, ScienceDirect, and Web of Science databases using keywords, such as "colorectal cancer" AND "phenolic compounds", "colorectal cancer" AND "polyphenol", "colorectal cancer" AND "phenolic acids", "colorectal cancer" AND "flavonoids", "colorectal cancer" AND "stilbene", and "colorectal cancer" AND "lignan" from the reputed peer-reviewed journals published over the last 20 years. Publications that incorporated in vivo experimental designs and produced statistically significant results were considered for this review. Many of these polyphenols demonstrate anti-CRC activities by inhibiting key cellular factors. This inhibition has been demonstrated by antiapoptotic effects, antiproliferative effects, or by upregulating factors responsible for cell cycle arrest or cell death in various in vivo CRC models. Numerous studies from independent laboratories have highlighted different plant phenolic compounds for their anti-CRC activities. While promising anti-CRC activity in many of these agents has created interest in this area, in-depth mechanistic and well-designed clinical studies are needed to support the therapeutic use of these compounds for the prevention and treatment of CRC.

Signaling pathways driving ocular malignancies and their targeting by bioactive phytochemicals.

Ocular cancers represent a rare pathology. The American Cancer Society estimates that 3,360 cases of ocular cancer occur annually in the United States. The major types of cancers of the eye include ocular melanoma (also known as uveal melanoma), ocular lymphoma, retinoblastoma, and squamous cell carcinoma. While uveal melanoma is one of the primary intraocular cancers with the highest occurrence in adults, retinoblastoma remains the most common primary intraocular cancer in children, and squamous cell carcinoma presents as the most common conjunctival cancer. The pathophysiology of these diseases involves specific cell signaling pathways. Oncogene mutations, tumor suppressor mutations, chromosome deletions/translocations and altered proteins are all described as causal events in developing ocular cancer. Without proper identification and treatment of these cancers, vision loss, cancer spread, and even death can occur. The current treatments for these cancers involve enucleation, radiation, excision, laser treatment, cryotherapy, immunotherapy, and chemotherapy. These treatments present a significant burden to the patient that includes a possible loss of vision and a myriad of side effects. Therefore, alternatives to traditional therapy are urgently needed. Intercepting the signaling pathways for these cancers with the use of naturally occurring phytochemicals could be a way to relieve both cancer burden and perhaps even prevent cancer occurrence. This research aims to present a comprehensive review of the signaling pathways involved in various ocular cancers, discuss current therapeutic options, and examine the potential of bioactive phytocompounds in the prevention and targeted treatment of ocular neoplasms. The current limitations, challenges, pitfalls, and future research directions are also discussed.

Type II lepra reaction--an unusual presentation.

Type II lepra reaction usually present with skin lesions. We report a 23 years old male patient presented with fever for two weeks with no visible skin lesion suggestive of leprosy and with no history of either completion or concurrent anti leprosy drug treatment was eventually turned out to be a case of Hansen's presenting with type II lepra reaction.

Metal-based Complexes as Potential Anti-cancer Agents.

Metal based therapy is no new in biomedical research. In early days, the biggest limitation was the inequality among therapeutical and toxicological dosages. Ever since, Barnett Rosenberg discovered cisplatin, a new era has begun to treat cancer with metal complexes. Platinum complexes such as oxaliplatin, cisplatin, and carboplatin, seem to be the foundation of metal/s-based components to challenge malignancies. With advancement in the biomolemoecular mechanism, researchers have started developing non-classical platinum-based complexes, where a different mechanistic approach of the complexes is observed towards the biomolecular target. Till date, larger numbers of metal/s-based complexes were synthesized by overhauling the present structures chemically by substituting the ligand or preparing the whole novel component with improved cytotoxic and safety profiles. Howsoever, due to elevated accentuation upon the therapeutic importance of metal/s-based components, a couple of those agents are at present in clinical trials and several other are in anticipating regulatory endorsement to enter the trial. This literature highlights the detailed heterometallic multinuclear components, primarily focusing on platinum, ruthenium, gold and remarks on possible stability, synergism, mechanistic studies and structure activity relationships.

Molecular Mechanisms of Action of Eugenol in Cancer: Recent Trends and Advancement.

BACKGROUND: Cancer is, at present, among the leading causes of morbidity globally. Despite advances in treatment regimens for cancer, patients suffer from poor prognoses. In this context, the availability of vast natural resources seems to alleviate the shortcomings of cancer chemotherapy. The last decade has seen a breakthrough in the investigations related to the anticancer potential of dietary phytoconstituents. Interestingly, a handsome number of bioactive principles, ranging from phenolic acids, phenylpropanoids, flavonoids, stilbenes, and terpenoids to organosulphur compounds have been screened for their anticancer properties. Among the phenylpropanoids currently under clinical studies for anticancer activity, eugenol is a promising candidate. Eugenol is effective against cancers like breast, cervical, lung, prostate, melanomas, leukemias, osteosarcomas, gliomas, etc., as evident from preclinical investigations. OBJECTIVE: The review aims to focus on cellular and molecular mechanisms of eugenol for cancer prevention and therapy. METHODS: Based on predetermined criteria, various scholarly repositories, including PubMed, Scopus, and Science Direct were analyzed for anticancer activities of eugenol. RESULTS: Different biochemical investigations reveal eugenol inducing cytotoxicity, inhibiting phases of the cell cycles, programmed cell death, and auto-phagocytosis in studied cancer lines; thus, portraying eugenol as a promising anticancer molecule. A survey of current literature has unveiled the molecular mechanisms intervened by eugenol in exercising its anticancer role. CONCLUSION: Based on the critical analysis of the literature, eugenol exhibits vivid signaling pathways to combat cancers of different origins. The reports also depict the advancement of novel nano-drug delivery approaches upgrading the therapeutic profile of eugenol. Therefore, eugenol nanoformulations may have enormous potential for both the treatment and prevention of cancer.

Role of γ-Secretase Inhibitors for the Treatment of Diverse Disease Conditions through Inhibition of Notch Signaling Pathway.

γ-secretase is an intramembrane protease sub-assembly that sunders transmembrane proteins. It is involved in intramembrane proteolysis and also contributes to the regeneration of transmembrane protein. The amyloid precursor proteins (APPs) are typical γ-secretase substrates. These proteins are cleaved to produce 36-43 amyloid-beta (Aß) amino acid peptides. Abnormal folding of these proteins fragments leads to amyloid plaques, which are frequently encountered in Alzheimer's disease. Some Type I class of integral membrane proteins is processed under the influence of γ-secretase, such as receptor tyrosine-protein kinase erbB4 and CD44 glycoprotein. γ-Secretase is being explored in several diseases as a clinical goal. Both γ-secretase inhibitors (GSIs) and γ-secretase modulators (GSMs) are being evaluated for this purpose. A large amount of γ-secretase inhibitors (GSIs) from peptide to non-peptide have been disclosed, offering several lead compounds for the design and optimization of γ-secretase targets, but most GSIs lack sufficient potency, exhibit low penetration in the brain, and manifest low selectiveness. γ-secretase inhibitors are obliquely a regulator of a γ-secretase substrate Notch, and valuable in the development of ß-amyloid peptide (Aß). These γ-secretase inhibitors block the Notch signaling pathway in autoimmune and lymphoproliferative disorders, like autoimmune lymphoproliferative syndrome (ALPS) and systemic lupus erythematosus (SLE), and perhaps even in cancerous cell proliferation, angiogenesis, and cellular differentiation of human-induced pluripotent stem cells (hiPSC). The current review portrays the mechanism, regulation, and inhibition of γ-secretase in the management of a wide assortment of diseases.

Myco-nanotechnological approach to synthesize silver oxide nanocuboids using endophytic fungus isolated from Citrus pseudolimon plant.

The current study reports the isolation of Colletotrichum plurivorum, an endophytic fungus from a Citrus pseudolimon plant and its utilization in the green synthesis of silver oxide nanocuboids (Ag2O NCs) at room temperature. The synthesized nanocrystals were thoroughly characterized by UV-vis, FTIR spectroscopy, field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), X-ray diffraction (XRD) analyses. Electron microscopic images confirmed the formation of cuboid shaped particles having size 200-250 nm in length and 80-150 nm in width, whereas, XRD and selected area electron diffraction (SAED) pattern confirms the formation of cubic Ag2O nanocrystals. Then these Ag2O NCs are applied in antibacterial activities against a pathogenic gram-negative bacteria Escherichia coli and gram-positive bacteria Bacillus subtilis and found very good activities against them. Currently these types of nanocuboids have drawn great interest in the field of catalysis, photocatalysis to biomedical applications.

Isatin: A Scaffold with Immense Biodiversity.

Isatin is an endogenous and a significant category of fused heterocyclic components and has widely been a part of several potential biologically useful synthetics. Since its discovery, tons of research work has been conducted with respect to the synthesis, chemical properties, and biological and industrial applications. It contains an indole nucleus having both lactam and keto moiety, which, while being a part of a molecular framework, exerted several biological effects, viz.; anti-microbial, anti-tubercular, anticonvulsant, anti-cancer, etc. Isatin derivatives are synthetically significant substrates, which can be utilized for the synthesis of huge diversified chemical entities of which few members emerged as drugs. The reason for this review is to provide extensive information pertaining to the chemistry and its significance in altering several pathological states of isatin and its derivatives. A Structure-Activity Relationship study thus developed through a gamut of scientific information indicates the importance of mostly electron-withdrawing groups, halogens, nitro, alkoxy, and, to a minor extent, groups with positive inductive effects, such as methyl at position 1, 5, 6 and 7 of isatin in alleviating several clinical conditions. It is also observed from the survey that the presence of two oxo groups at positions 2 and 3 sometimes becomes insignificant as a fusion with a heterocycle at these positions resulted in a biologically relevant compound.