Ursolic acid: a natural modulator of signaling networks in different cancers.

Incidence rate of cancer is estimated to increase by 40% in 2030. Furthermore, the development of resistance against currently available treatment strategies has contributed to the cancer-associated mortality. Scientists are now looking for the solutions that could help prevent the disease occurrence and could provide a pain-free treatment alternative for cancers. Therefore, efforts are now put to find a potent natural compound that could sever this purpose. Ursolic acid (UA), a triterpene acid, has potential to inhibit the tumor progression and induce sensitization to conventional treatment drugs has been documented. Though, UA is a hydrophobic compound therefore it is usually chemically modified to increase its bioavailability prior to administration. However, a thorough literature indicating its mechanism of action and limitations for its use at clinical level was not reviewed. Therefore, the current study was designed to highlight the potential mechanism of UA, its anti-cancer properties, and potential applications as therapeutic compound. This endeavour is a valuable contribution in understanding the hurdles preventing the translation of its potential at clinical level and provides foundations to design new studies that could help enhance its bioavailability and anti-cancer potential for various cancers.

The crucial role of prolactin-lactogenic hormone in Covid-19.

Prolactin (PRL) is a peptide hormone secreted from anterior pituitary involved in milk production in the females and regulation of sex drive in both sexes. PRL has pro-inflammatory and anti-inflammatory functions. High PRL serum level or hyperprolactinemia is associated with different viral infections. In coronavirus disease 2019 (Covid-19), which caused by positive-sense single-strand RNA virus known as severe acute respiratory distress syndrome coronavirus type 2 (SARS-CoV-2), PRL serum level is increased. PRL in Covid-19 may exacerbate the underlying inflammatory status by induction release of pro-inflammatory cytokines. However, PRL through its anti-inflammatory effects may reduce the hyperinflammatory status in Covid-19. The underlying mechanism of increasing PRL in Covid-19 is poorly understood. Therefore, in this review we try to find the potential anti-inflammatory or pro-inflammatory role of PRL in Covid-19. As well, this review was aimed to discuss the underlying causes and mechanisms for Covid-19-induced hyperprolactinemia.

Hesperetin's health potential: moving from preclinical to clinical evidence and bioavailability issues, to upcoming strategies to overcome current limitations.

Flavonoids are common in the plant kingdom and many of them have shown a wide spectrum of bioactive properties. Hesperetin (Hst), the aglycone form of hesperidin, is a great example, and is the most abundant flavonoid found in Citrus plants. This review aims to provide an overview on the in vitro, in vivo and clinical studies reporting the Hst pharmacological effects and to discuss the bioavailability-related issues. Preclinical studies have shown promising effects on cancer, cardiovascular diseases, carbohydrate dysregulation, bone health, and other pathologies. Clinical studies have supported the Hst promissory effects as cardioprotective and neuroprotective agent. However, further well-designed clinical trials are needed to address the other Hst effects observed in preclinical trials, as well as to a more in-depth understanding of its safety profile.

Flavonoids as potential anti-platelet aggregation agents: from biochemistry to health promoting abilities.

Cardiovascular ailments are the number one cause of mortalities throughout the globe with 17.9 million deaths per year. Platelet activation and aggregation play a crucial role in the pathogenesis of arterial diseases, including acute coronary syndrome, acute myocardial infarction, cerebrovascular transient ischemia, unstable angina, among others. Flavonoids-rich plant extracts are gaining interest for treating the heart-related problems due to safe nature of these herbal extracts. Consumption of plant-food-derived bioactives, particularly flavonoids, has shown antithrombotic, and cardiovascular protective effects due to its anti-platelet activity. Preclinical and clinical trials have proven that flavonoid-rich plant extracts are protective against the cardiac ailments through anti-platelet aggregation activity. This review aims to highlight the anti-platelet aggregation potential of flavonoids with a key emphasis on the therapeutic efficacy in humans. The mechanism of flavonoids in preventing and treating cardiovascular diseases is also highlighted based on preclinical and clinical experimental trials. Further studies are the need of time for exploring the exact molecular mechanism of flavonoids as anti-platelet aggregation agents for treating heart-related problems.

Natural Compounds and Products from an Anti-Aging Perspective.

Aging is a very complex process that is accompanied by a degenerative impairment in many of the major functions of the human body over time. This inevitable process is influenced by hereditary factors, lifestyle, and environmental influences such as xenobiotic pollution, infectious agents, UV radiation, diet-borne toxins, and so on. Many external and internal signs and symptoms are related with the aging process and senescence, including skin dryness and wrinkles, atherosclerosis, diabetes, neurodegenerative disorders, cancer, etc. Oxidative stress, a consequence of the imbalance between pro- and antioxidants, is one of the main provoking factors causing aging-related damages and concerns, due to the generation of highly reactive byproducts such as reactive oxygen and nitrogen species during the metabolism, which result in cellular damage and apoptosis. Antioxidants can prevent these processes and extend healthy longevity due to the ability to inhibit the formation of free radicals or interrupt their propagation, thereby lowering the level of oxidative stress. This review focuses on supporting the antioxidant system of the organism by balancing the diet through the consumption of the necessary amount of natural ingredients, including vitamins, minerals, polyunsaturated fatty acids (PUFA), essential amino acids, probiotics, plants' fibers, nutritional supplements, polyphenols, some phytoextracts, and drinking water.

Cytotoxicity of synthetic derivatives against breast cancer and multi-drug resistant breast cancer cell lines: a literature-based perspective study.

Cancer is the second most killer worldwide causing millions of people to lose their lives every year. In the case of women, breast cancer takes away the highest proportion of mortality rate than other cancers. Due to the mutation and resistance-building capacity of different breast cancer cell lines against conventional therapies, this death rate is on the verge of growth. New effective therapeutic compounds and treatment method is the best way to look out for in this critical time. For instance, new synthetic derivatives/ analogues synthesized from different compounds can be a ray of hope. Numerous synthetic compounds have been seen enhancing the apoptosis and autophagic pathway that directly exerts cytotoxicity towards different breast cancer cell lines. To cease the ever-growing resistance of multi-drug resistant cells against anti-breast cancer drugs (Doxorubicin, verapamil, tamoxifen) synthetic compounds may play a vital role by increasing effectivity, showing synergistic action. Many recent and previous studies have reported that synthetic derivatives hold potentials as an effective anti-breast cancer agent as they show great cytotoxicity towards cancer cells, thus can be used even vastly in the future in the field of breast cancer treatment. This review aims to identify the anti-breast cancer properties of several synthetic derivatives against different breast cancer and multi-drug-resistant breast cancer cell lines with their reported mechanism of action and effectivity.

Apigenin role as cell-signaling pathways modulator: implications in cancer prevention and treatment.

Cancer is a complex disease orchestrated by various extrinsic and intrinsic pathways. In recent years, there has been a keen interest towards the development of natural extracts-based cancer therapeutics with minimum adverse effects. In pursuit of effective strategy, a wide variety of natural products-derived compounds have been addressed for their anticancer effects. Apigenin is a naturally-occurring flavonoid present abundantly in various fruits and vegetables. Decades of research have delineated the pharmacological and biological properties of apigenin. Specifically, the apigenin-mediated anticancer activities have been documented in various types of cancer, but the generalized scientific evidence encompassing various molecular interactions and processes, such as regulation of the apoptotic machinery, aberrant cell signaling and oncogenic protein network have not been comprehensively covered. In this sense, in this review we have attempted to focus on the apigenin-mediated regulation of oncogenic pathways in various cancers. We have also addressed the cutting-edge research which has unveiled the remarkable abilities of apigenin to interact with microRNAs to modulate key cellular processes, with special emphasis on the nano-formulations of apigenin that can help their targeted delivery and can be a therapeutic solution for the treatment of various cancers.

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers.

Cancers are complex diseases orchestrated by a plethora of extrinsic and intrinsic factors. Research spanning over several decades has provided better understanding of complex molecular interactions responsible for the multifaceted nature of cancer. Recent advances in the field of next generation sequencing and functional genomics have brought us closer towards unravelling the complexities of tumor microenvironment (tumor heterogeneity) and deregulated signaling cascades responsible for proliferation and survival of tumor cells. Phytochemicals have begun to emerge as potent beneficial substances aimed to target deregulated signaling pathways. Isoflavonoid genistein is an essential phytochemical involved in regulation of key biological processes including those in different types of cancer. Emerging preclinical evidence have shown its anti-cancer, anti-inflammatory and anti-oxidant properties. Testing of this substance is in various phases of clinical trials. Comprehensive preclinical and clinical trials data is providing insight on genistein as a modulator of various signaling pathways both at transcription and translation levels. In this review we have explained the mechanistic regulation of several key cellular pathways by genistein. We have also addressed in detail various microRNAs regulated by genistein in different types of cancer. Moreover, application of nano-formulations to increase the efficiency of genistein is also discussed. Understanding the pleiotropic potential of genistein to regulate key cellular pathways and development of efficient drug delivery system will bring us a step towards designing better chemotherapeutics.

Chitosan nanoparticles as a promising tool in nanomedicine with particular emphasis on oncological treatment.

The study describes the current state of knowledge on nanotechnology and its utilization in medicine. The focus in this manuscript was on the properties, usage safety, and potentially valuable applications of chitosan-based nanomaterials. Chitosan nanoparticles have high importance in nanomedicine, biomedical engineering, discovery and development of new drugs. The manuscript reviewed the new studies regarding the use of chitosan-based nanoparticles for creating new release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity of drugs. Nowadays, effective cancer treatment is a global problem, and recent advances in nanomedicine are of great importance. Special attention was put on the application of chitosan nanoparticles in developing new system for anticancer drug delivery. Pre-clinical and clinical studies support the use of chitosan-based nanoparticles in nanomedicine. This manuscript overviews the last progresses regarding the utilization, stability, and bioavailability of drug nanoencapsulation with chitosan and their safety.

Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis.

A fundamental metabolic feature of cancerous tissues is high glucose consumption. The rate of glucose consumption in a cancer cell can be 10-15 times higher than in normal cells. Isolation and cultivation of tumor cells in vitro highlight properties that are associated with intensive glucose utilization, the presence of minimal oxidative metabolism, an increase in lactate concentrations in the culture medium and a reduced rate of oxygen consumption. Although glycolysis is suggested as a general feature of malignant cells and recently identified as a possible contributing factor to tumor progression, several studies highlight distinct metabolic characteristics in some tumors, including a relative decrease in avidity compared to glucose and/or a glutamine dependency of lactate and even proliferative tumor cells. The aim of this review is to determine the particularities in the energy metabolism of cancer cells, focusing on the main nutritional substrates, such as glucose and glutamine, evaluating lactate dehydrogenase as a potential marker of malignancy and estimating activators and inhibitors in cancer treatment.

Phytotherapy and food applications from Brassica genus.

Plants of the genus Brassica occupy the top place among vegetables in the world. This genus, which contains a group of six related species of a global economic significance, three of which are diploid: Brassica nigra (L.) K. Koch, Brassica oleracea L., and Brassica rapa L. and three are amphidiploid species: Brassica carinata A. Braun, Brassica juncea (L.) Czern., and Brassica napus L. These varieties are divided into oily, fodder, spice, and vegetable based on their morphological structure, chemical composition, and usefulness of plant organs. The present review provides information about habitat, phytochemical composition, and the bioactive potential of Brassica plants, mainly antioxidant, antimicrobial, anticancer activities, and clinical studies in human. Brassica vegetables are of great economic importance around the world. At present, Brassica plants are grown together with cereals and form the basis of global food supplies. They are distinguished by high nutritional properties from other vegetable plants, such as low fat and protein content and high value of vitamins, fibers along with minerals. In addition, they possess several phenolic compounds and have a unique type of compounds namely glucosinolates that differentiate these crops from other vegetables. These compounds are also responsible for numerous biological activities to the genus Brassica as described in this review.

Sulfhydryl groups as targets of mercury toxicity.

The present study addresses existing data on the affinity and conjugation of sulfhydryl (thiol; -SH) groups of low- and high-molecular-weight biological ligands with mercury (Hg). The consequences of these interactions with special emphasis on pathways of Hg toxicity are highlighted. Cysteine (Cys) is considered the primary target of Hg, and link its sensitivity with thiol groups and cellular damage. In vivo, Hg complexes play a key role in Hg metabolism. Due to the increased affinity of Hg to SH groups in Cys residues, glutathione (GSH) is reactive. The geometry of Hg(II) glutathionates is less understood than that with Cys. Both Cys and GSH Hg-conjugates are important in Hg transport. The binding of Hg to Cys mediates multiple toxic effects of Hg, especially inhibitory effects on enzymes and other proteins that contain free Cys residues. In blood plasma, albumin is the main Hg-binding (Hg2+, CH3Hg+, C2H5Hg+, C6H5Hg+) protein. At the Cys34 residue, Hg2+ binds to albumin, whereas other metals likely are bound at the N-terminal site and multi-metal binding sites. In addition to albumin, Hg binds to multiple Cys-containing enzymes (including manganese-superoxide dismutase (Mn-SOD), arginase I, sorbitol dehydrogenase, and δ-aminolevulinate dehydratase, etc.) involved in multiple processes. The affinity of Hg for thiol groups may also underlie the pathways of Hg toxicity. In particular, Hg-SH may contribute to apoptosis modulation by interfering with Akt/CREB, Keap1/Nrf2, NF-κB, and mitochondrial pathways. Mercury-induced oxidative stress may ensue from Cys-Hg binding and inhibition of Mn-SOD (Cys196), thioredoxin reductase (TrxR) (Cys497) activity, as well as limiting GSH (GS-HgCH3) and Trx (Cys32, 35, 62, 65, 73) availability. Moreover, Hg-thiol interaction also is crucial in the neurotoxicity of Hg by modulating the cytoskeleton and neuronal receptors, to name a few. However, existing data on the role of Hg-SH binding in the Hg toxicity remains poorly defined. Therefore, more research is needed to understand better the role of Hg-thiol binding in the molecular pathways of Hg toxicology and the critical role of thiols to counteract negative effects of Hg overload.

Chronic pelvic pain syndrome: Highlighting medicinal plants toward biomolecules discovery for upcoming drugs formulation.

Chronic pelvic pain syndrome (CPPS) can be triggered by a various types of gynecological, gastrointestinal, urological, and musculoskeletal disorders. Recently, the role of the central nervous system has proven to be an integral part on the development of any chronic pain syndrome, including CPPS. However, owing to the complex and heterogeneous etiology and pathophysiology of CPPS, the establishment of effective therapeutic interventions remains challenging for both physicians and patients. Nonetheless, recent studies have pointed that medicinal plants and their secondary metabolites can be effectively used in CPPS therapy, besides contributing to restore the patients' quality of life and potentiate the conventional CPPS management. In this sense, this review aims to provide a careful overview on the biomedical data for the use of medicinal plants use and their secondary metabolites on CPPS management.

Symphytum Species: A Comprehensive Review on Chemical Composition, Food Applications and Phytopharmacology.

Symphytum species belongs to the Boraginaceae family and have been used for centuries for bone breakages, sprains and rheumatism, liver problems, gastritis, ulcers, skin problems, joint pain and contusions, wounds, gout, hematomas and thrombophlebitis. Considering the innumerable potentialities of the Symphytum species and their widespread use in the world, it is extremely important to provide data compiling the available literature to identify the areas of intense research and the main gaps in order to design future studies. The present review aims at summarizing the main data on the therapeutic indications of the Symphytum species based on the current evidence, also emphasizing data on both the efficacy and adverse effects. The present review was carried out by consulting PubMed (Medline), Web of Science, Embase, Scopus, Cochrane Database, Science Direct and Google Scholar (as a search engine) databases to retrieve the most updated articles on this topic. All articles were carefully analyzed by the authors to assess their strengths and weaknesses, and to select the most useful ones for the purpose of review, prioritizing articles published from 1956 to 2018. The pharmacological effects of the Symphytum species are attributed to several chemical compounds, among them allantoin, phenolic compounds, glycopeptides, polysaccharides and some toxic pyrrolizidine alkaloids. Not less important to highlight are the risks associated with its use. In fact, there is increasing consumption of over-the-counter drugs, which when associated with conventional drugs can cause serious and even fatal adverse events. Although clinical trials sustain the folk topical application of Symphytum species in musculoskeletal and blunt injuries, with minor adverse effects, its antimicrobial potency was still poorly investigated. Further studies are needed to assess the antimicrobial spectrum of Symphytum species and to characterize the active molecules both in vitro and in vivo.

Iron-related Biomarkers in the Diagnosis and Management of Iron Disorders.

BACKGROUND: Iron deficiency and iron-related disorders are common health issues worldwide, affecting a significant proportion of the population. Diagnosis and management of these disorders rely heavily on using various iron-related biomarkers that can provide valuable clinical information. OBJECTIVE: This review article provides an overview of the most commonly used iron-related biomarkers, including serum ferritin, transferrin saturation, soluble transferrin receptor, zinc protoporphyrin, and free erythrocyte protoporphyrin. Other emerging biomarkers, such as hepcidin and retinol-binding protein 4, are also discussed. RESULTS: Iron plays a vital role in various physiological processes, including oxygen transport, energy metabolism, and DNA synthesis. The article highlights the advantages and limitations of iron biomarkers and their clinical applications in diagnosing and managing iron deficiency and iron-related anemia. CONCLUSION: Using iron-related biomarkers in screening and monitoring programs can improve patient outcomes and reduce healthcare costs.

Koetjapic acid: unveiling its potential as a saviour in the realm of biological and medicinal properties, with a focus on anticancer mechanism of action.

Scientists have been compelled to search for alternative treatments due to the increasing prevalence of chemoresistance as well as the agonising and distressing side effects of both chemotherapy and radiation. Plant extracts have been exploited to treat various medical conditions for ages. Considering this fact, the main focus of various recent studies that are being conducted to find new and potent anticancer drugs involves the identification and utilisation of potential therapeutic chemicals present in plant extracts. Koetjapic acid (KJA), which belongs to the family of triterpenes, is primarily isolated from Sandoricum koetjape. Ongoing investigations into its therapeutic applications have revealed its tendency to impede the growth and proliferation of cancer cells. Koetjapic acid activates the intrinsic apoptotic pathway and promotes the death of cancer cells. Moreover, it inhibits angiogenesis and the dissemination of tumour (metastasis) by targeting the VEGF signalling cascade. Therefore, this study aims to elucidate the underlying mechanism of anticancer activity of koetjapic acid, providing significant insight into the compound's potential as an anticancer agent.

Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy - A comprehensive review.

Cancer incidences are rising each year. In 2020, approximately 20 million new cancer cases and 10 million cancer-related deaths were recorded. The World Health Organization (WHO) predicts that by 2024 the incidence of cancer will increase to 30.2 million individuals annually. Considering the invasive characteristics of its diagnostic procedures and therapeutic methods side effects, scientists are searching for different solutions, including using plant-derived bioactive compounds, that could reduce the probability of cancer occurrence and make its treatment more comfortable. In this regard, oridonin (ORI), an ent-kaurane diterpenoid, naturally found in the leaves of Rabdosia rubescens species, has been found to have antitumor, antiangiogenesis, antiasthmatic, antiinflammatory, and apoptosis induction properties. Extensive research has been performed on ORI to find various mechanisms involved in its anticancer activities. This review article provides an overview of ORI's effectiveness on murine and human cancer populations from 1976 to 2022 and provides insight into the future application of ORI in different cancer therapies.

Anti-cancer properties of boswellic acids: mechanism of action as anti-cancerous agent.

With the advent of highly effective plant-based medications with few or no side effects, the use of phytomedicines against complex diseases such as cancer is becoming more widespread. The broadly recognized pentacyclic triterpenes known as boswellic acids (BAs) are derived from the oleogum resin, or frankincense, extracted from the plant species of the genus Boswellia. The frankincense mixture contains various BA types, each having a different potential and helping treat certain cancers. This review focuses on details regarding the traits of the BAs, their roles as anti-cancer agents, the mechanism underlying their activities, and the function of their semi-synthetic derivatives in managing and treating certain cancers. The review also explores the biological sources of BAs, how they are conserved, and how biotechnology might help preserve and improve in vitro BA production. The review concludes that the BAs and their semi-synthetic derivatives are effective against a broad spectrum of cancer cell lines. The detailed information in the review can be helpful for researchers to gain more information about BAs and BA-based medications for efficient and cost-effective cancer treatments.

New insights into the anticancer therapeutic potential of maytansine and its derivatives.

Maytansine is a pharmacologically active 19-membered ansamacrolide derived from various medicinal plants and microorganisms. Among the most studied pharmacological activities of maytansine over the past few decades are anticancer and anti-bacterial effects. The anticancer mechanism of action is primarily mediated through interaction with the tubulin thereby inhibiting the assembly of microtubules. This ultimately leads to decreased stability of microtubule dynamics and cause cell cycle arrest, resulting in apoptosis. Despite its potent pharmacological effects, the therapeutic applications of maytansine in clinical medicine are quite limited due to its non-selective cytotoxicity. To overcome these limitations, several derivatives have been designed and developed mostly by modifying the parent structural skeleton of maytansine. These structural derivatives exhibit improved pharmacological activities as compared to maytansine. The present review provides a valuable insight into maytansine and its synthetic derivatives as anticancer agents.