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

Icaritin is a natural prenylated flavonoid derived from the Chinese herb Epimedium. The compound has shown antitumor effects in various cancers, especially hepatocellular carcinoma (HCC). Icaritin exerts its anticancer activity by modulating multiple signaling pathways, such as IL-6/JAK/STAT3, ER-α36, and NF-κB, affecting the tumor microenvironment and immune system. Several clinical trials have evaluated the safety and efficacy of icaritin in advanced HCC patients with poor prognoses, who are unsuitable for conventional therapies. The results have demonstrated that icaritin can improve survival, delay progression, and produce clinical benefits in these patients, with a favorable safety profile and minimal adverse events. Moreover, icaritin can enhance the antitumor immune response by regulating the function and phenotype of various immune cells, such as CD8+ T cells, MDSCs, neutrophils, and macrophages. These findings suggest that icaritin is a promising candidate for immunotherapy in HCC and other cancers. However, further studies are needed to elucidate the molecular mechanisms and optimal dosing regimens of icaritin and its potential synergistic effects with other agents. Therefore, this comprehensive review of the scientific literature aims to summarize advances in the knowledge of icaritin in preclinical and clinical studies as well as the pharmacokinetic, metabolism, toxicity, and mechanisms action to recognize the main challenge, gaps, and opportunities to develop a medication that cancer patients can use. Thus, our main objective was to clarify the current state of icaritin for use as an anticancer drug.

Bioactivities of morroniside: A comprehensive review of pharmacological properties and molecular mechanisms.

Morroniside (MOR) is an iridoid glycoside and the main active principle of the medicinal plant, Cornus officinalis Sieb. This phytochemical is associated with numerous health benefits due to its antioxidant properties. The primary objective of the present study was to assess the pharmacological effects and underlying mechanisms of MOR, utilizing published data obtained from literature databases. Data collection involved accessing various sources, including PubMed/Medline, Scopus, Science Direct, Google Scholar, Web of Science, and SpringerLink. Our findings demonstrate that MOR can be utilized for the treatment of several diseases and disorders, as numerous studies have revealed its significant therapeutic activities. These activities encompass anti-inflammatory, antidiabetic, lipid-lowering capability, anticancer, trichogenic, hepatoprotective, gastroprotective, osteoprotective, renoprotective, and cardioprotective effects. MOR has also shown promising benefits against various neurological ailments, including Alzheimer's disease, Parkinson's disease, spinal cord injury, cerebral ischemia, and neuropathic pain. Considering these therapeutic features, MOR holds promise as a lead compound for the treatment of various ailments and disorders. However, further comprehensive preclinical and clinical trials are required to establish MOR as an effective and reliable therapeutic agent.

Ginsenoside Rg5 as an anticancer drug: a comprehensive review on mechanisms, structure-activity relationship, and prospects for clinical advancement.

Cancer remains one of the leading causes of death in the world. Despite the considerable success of conventional treatment strategies, the incidence and mortality rates are still high, making developing new effective anticancer therapies an urgent priority. Ginsenoside Rg5 (Rg5) is a minor ginsenoside constituent obtained exclusively from ginseng species and is known for its broad spectrum of pharmacological activities. This article aimed to comprehensively review the anticancer properties of Rg5, focusing on action mechanisms, structure-activity relationship (SAR), and pharmacokinetics attributes. The in vitro and in vivo activities of Rg5 have been proven against several cancer types, such as breast, liver, lung, bone, and gastrointestinal (GI) cancers. The modulation of multiple signaling pathways critical for cancer growth and survival mediates these activities. Nevertheless, human clinical studies of Rg5 have not been addressed before, and there is still considerable ambiguity regarding its pharmacokinetics properties. In addition, a significant shortage in the structure-activity relationship (SAR) of Rg5 has been identified. Therefore, future efforts should focus on further optimization by performing extensive SAR studies to uncover the structural features essential for the potent anticancer activity of Rg5. Thus, this review highlights the value of Rg5 as a potential anticancer drug candidate and identifies the research areas requiring more investigation.

Current stage of preclinical and clinical development of guggulsterone in cancers: Challenges and promises.

Throughout human history, the utilization of medicinal herbs has been recognized as a crucial defense against various ailments, including cancer. Natural products with potential anticancer properties, capable of inducing apoptosis in cancer cells, have garnered substantial attention. One such agent under investigation is guggulsterone (GS), a phytosterol derived from the gum resin of the Commiphora mukul tree. This review aims to provide a comprehensive summary of recent studies elucidating the anticancer molecular mechanisms and molecular targets of GS, guiding future research and potential applications as an adjuvant drug in cancer therapy. Recent in vivo and in vitro studies have explored the biological activities of the active ingredients in Commiphora mukul. Specifically, GS emerges as a potential cancer chemopreventive and therapeutic agent. The investigations delve into the impact of GS on constitutively activated survival pathways, including Janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear factor-kappa B (NF-kB), and PI3-kinase/AKT signaling pathways. These pathways regulate antiapoptotic and proinflammatory genes, exerting control over growth and inflammatory responses. The findings highlight the potential of GS in disrupting survival pathways crucial for cancer cell viability. The inhibition of JAK/STAT, NF-kB, and PI3-kinase/AKT signaling pathways positions GS as a promising candidate for cancer therapy. The review synthesizes evidence from diverse studies, underscoring the multifaceted biological activities of GS in cancer prevention and treatment. To advance our understanding, future clinical and translational studies are imperative to determine effective doses in humans. Additionally, there is a need for the development of new pharmaceutical forms of GS to optimize therapeutic effects. This comprehensive review provides a foundation for ongoing research, offering insights into the potential of GS as a valuable addition to the armamentarium against cancer.

Glucosinolates in cancer prevention and treatment: experimental and clinical evidence.

Glucosinolates are naturally occurring ß-d-thioglucosides that mainly exist in the Brassicaceae family. The enzyme myrosinase hydrolyzes glucosinolates to form isothiocyanates, which are chemical protectors. Phenethyl isothiocyanate, sulforaphane, and benzyl isothiocyanate are potential isothiocyanate with efficient anti-cancer effects as a protective or treatment agent. Glucosinolate metabolites exert the cancer-preventive activity through different mechanisms, including induction of the Nrf2 transcription factor, inhibition of expression of tumor necrosis factor-α (TNFα) and interleukin-1ß (IL-1ß), induction of apoptosis through inhibiting phase I enzymes and inducting phase II enzymes, interruption of caspase pathways, STAT1/STAT2, inhibition of sulfotransferases. Moreover, glucosinolates and their metabolites are effective in cancer treatment by inhibiting angiogenesis, upregulating natural killers, increasing expression of p53, p21, caspase 3 and 9, and modulating NF-κB. Despite the mentioned cancer-preventing effects, some isothiocyanates can increase the risk of tumors. So, further studies are needed to obtain an accurate and effective dose for each glucosinolates to treat different types of tumors.

Amelioration of pain and anxiety in sleep-deprived rats by intra-amygdala injection of cinnamaldehyde.

Background: Sleep disorders are accompanied by increased anxiety and somatic pain. In addition, it has been observed that anxiety and pain have a boosting effect on each other, resulting in continued sleep disturbances. Amygdala's (CeA) central nucleus plays a crucial role in these processes. Cinnamaldehyde (Cinn) is an aromatic compound with anti-anxiety, antioxidant, and sleep-promoting properties. The present study uses sleep-deprived rats to examine the effects of an intra-CeA injection of Cinn on pain and anxiety. Methods: Sleep deprivation (SD) was induced using the platform technique. 35 male Wistar rats were divided into five groups. Anxiety state and nociception were evaluated among groups using formalin test (F.T.), open field test (OFT), and elevated plus maze (EPM). Anxiety tests (OFT and EPM) were conducted in all groups. The first group was undergone FT without induction of SD (SD-FT+). The second group received SD without FT(SD+FT-). The third group received both SD and FT(SD+FT+). The treatment and vehicle groups have undergone both SD and FT in addition to the respectively intra-CeA injection of Cinn (SD+FT+ Cinn) and Cinn vehicle (SD+FT+ VC). The recorded behaviors were analyzed between groups using IBM SPSS 24th version. Results: SD did not lead to any significant difference in nociceptive behaviors in FT between groups SD-FT+ and SD+FT+ (P ≥ 0.05). At the same time, there was a considerable discrepancy in rearing behaviors (P < 0.006) and the number of fecal boli (P < 0.004) recorded in OFM between these groups. Treatment with Cinn led to decreased nociception (P < 0.038), decreased rearing behaviors (P < 0.01), and reduced defecation (P < 0.004) in group SD + FT+ Cinn in comparison to the group SD+FT+. There were no differences in anxiety test results between the first and second groups (P ≥ 0.05). Conclusion: SD can lead to elevated anxiety, while intra-CeA injection of Cinn ameliorated both perceptions of acute pain and anxiety. Besides, the conduction of FT before the anxiety test led to no disturbance in the results of anxiety tests.

Neopeltolide and its synthetic derivatives: a promising new class of anticancer agents.

Being the first or second cause of death worldwide, cancer represents the most significant clinical, social, and financial burden of any human illness. Despite recent progresses in cancer diagnosis and management, traditional cancer chemotherapies have shown several adverse side effects and loss of potency due to increased resistance. As a result, one of the current approaches is on with the search of bioactive anticancer compounds from natural sources. Neopeltolide is a marine-derived macrolide isolated from deep-water sponges collected off Jamaica's north coast. Its mechanism of action is still under research but represents a potentially promising novel drug for cancer therapy. In this review, we first illustrate the general structural characterization of neopeltolide, the semi-synthetic derivatives, and current medical applications. In addition, we reviewed its anticancer properties, primarily based on in vitro studies, and the possible clinical trials. Finally, we summarize the recent progress in the mechanism of antitumor action of neopeltolide. According to the information presented, we identified two principal challenges in the research, i) the effective dose which acts neopeltolide as an anticancer compound, and ii) to unequivocally establish the mechanism of action by which the compound exerts its antiproliferative effect.

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.

Therapeutic strategies for rheumatic diseases and disorders: targeting redox imbalance and oxidative stress.

Rheumatic diseases and disorders (RDDs) are a group of chronic autoimmune diseases that are collectively called "multicausal diseases". They have resulted from predisposing genetic profiles and exposure to a range of environmental, occupational and lifestyle risk factors. Other causative factors include bacterial and viral attacks, sexual habits, trauma, etc. In addition, numerous studies reported that redox imbalance is one of the most serious consequences of RDDs. For example, rheumatoid arthritis (RA) as a classic example of chronic RDDs is linked to oxidative stress. This paper summarizes the contributions of redox imbalance to RDDs. The findings suggest that establishing direct or indirect therapeutic strategies for RDDs requires a more in-depth understanding of the redox dysregulation in these diseases. For example, the recent awareness of the roles of peroxiredoxins (Prdxs, e.g. Prdx2, Prdx3) in RDDs provided one potential route of therapeutic intervention of these pathologies. Changes in stressful lifestyles and dietary habits may also provide additional benefits in the management of RDDs. Future studies should be directed to explore molecular interactions in redox regulations associated with RDDS and potential therapeutic interventions.

Medicinal and mechanistic overview of artemisinin in the treatment of human diseases.

Artemisinin (ART) is a bioactive compound isolated from the plant Artemisia annua and has been traditionally used to treat conditions such as malaria, cancer, viral infections, bacterial infections, and some cardiovascular diseases, especially in Asia, North America, Europe and other parts of the world. This comprehensive review aims to update the biomedical potential of ART and its derivatives for treating human diseases highlighting its pharmacokinetic and pharmacological properties based on the results of experimental pharmacological studies in vitro and in vivo. Cellular and molecular mechanisms of action, tested doses and toxic effects of artemisinin were also described. The analysis of data based on an up-to-date literature search showed that ART and its derivatives display anticancer effects along with a wide range of pharmacological activities such as antibacterial, antiviral, antimalarial, antioxidant and cardioprotective effects. These compounds have great potential for discovering new drugs used as adjunctive therapies in cancer and various other diseases. Detailed translational and experimental studies are however needed to fully understand the pharmacological effects of these compounds.

An updated overview of cyanidins for chemoprevention and cancer therapy.

Anthocyanins are colored polyphenolic compounds that belong to the flavonoids family and are largely present in many vegetables and fruits. They have been used in traditional medicine in many cultures for a long time. The most common and abundant anthocyanins are those presenting an O-glycosylation at C-3 (C ring) of the flavonoid skeleton to form -O-ß-glucoside derivatives. The present comprehensive review summarized recent data on the anticancer properties of cyanidings along with natural sources, phytochemical data, traditional medical applications, molecular mechanisms and recent nanostrategies to increase the bioavailability and anticancer effects of cyanidins. For this analysis, in vitro, in vivo and clinical studies published up to the year 2022 were sourced from scientific databases and search engines such as PubMed/Medline, Google scholar, Web of Science, Scopus, Wiley and TRIP database. Cyanidins' antitumor properties are exerted during different stages of carcinogenesis and are based on a wide variety of biological activities. The data gathered and discussed in this review allows for affirming that cyanidins have relevant anticancer activity in vitro, in vivo and clinical studies. Future research should focus on studies that bring new data on improving the bioavailability of anthocyanins and on conducting detailed translational pharmacological studies to accurately establish the effective anticancer dose in humans as well as the correct route of administration.

Anti-Inflammatory Therapeutic Mechanisms of Natural Products: Insight from Rosemary Diterpenes, Carnosic Acid and Carnosol.

Carnosic acid (CA) and carnosol (CAR) are two major diterpenes of the rosemary plant (Rosmarinus officinalis). They possess a phenolic structural moiety and are endowed with the power to remove cellular reactive oxygen species (ROS) either through direct scavenging reaction or indirectly through upregulation of antioxidant defences. Hand in hand with these activities are their multiple biological effects and therapeutic potential orchestrated through modulating various signalling pathways of inflammation, including the NF-κB, MAPK, Nrf2, SIRT1, STAT3 and NLRP3 inflammasomes, among others. Consequently, they ameliorate the expression of pro-inflammatory cytokines (e.g., TNF-α, IL-1 and IL-6), adhesion molecules, chemokines and prostaglandins. These anti-inflammatory mechanisms of action as a therapeutic link to various effects of these compounds, as in many other natural products, are scrutinised.

The Molecular Pharmacology of Phloretin: Anti-Inflammatory Mechanisms of Action.

The isolation of phlorizin from the bark of an apple tree in 1835 led to a flurry of research on its inhibitory effect on glucose transporters in the intestine and kidney. Using phlorizin as a prototype drug, antidiabetic agents with more selective inhibitory activity towards glucose transport at the kidney have subsequently been developed. In contrast, its hydrolysis product in the body, phloretin, which is also found in the apple plant, has weak antidiabetic properties. Phloretin, however, displays a range of pharmacological effects including antibacterial, anticancer, and cellular and organ protective properties both in vitro and in vivo. In this communication, the molecular basis of its anti-inflammatory mechanisms that attribute to its pharmacological effects is scrutinised. These include inhibiting the signalling pathways of inflammatory mediators' expression that support its suppressive effect in immune cells overactivation, obesity-induced inflammation, arthritis, endothelial, myocardial, hepatic, renal and lung injury, and inflammation in the gut, skin, and nervous system, among others.

Putative Therapeutic Impact of Inflammasome Inhibitors against COVID-19-Induced ARDS.

Given the importance of COVID-19-induced ARDS, recently, researchers have strived to determine underlying mechanisms involved in the inflammatory responses. In this regard, inflammasomes possess a distinct priority for cytokine storm occurrence and, subsequently, ARDS progression in ill patients with SARS-CoV-2 infection. In this minireview, the characteristics of known inflammasome inhibitors and designed research in this field were concretely deciphered.

The anti-Trypanosoma activities of medicinal plants: A systematic review of the literature.

BACKGROUND: The existing drug treatments for trypanosomiases are limited and suffer from shortcomings due to their toxicity and the emergence of resistant parasites. Developing anti-trypanosomal compounds based on natural products is a promising way of fighting trypanosomiases. OBJECTIVES: This study aims to identify through scientific review a large variety of medicinal plants (anti-trypanosomal) used worldwide and scientifically shown to display anti-trypanosomal effects. METHODS: To collect data, the anti-trypanosomal activities of Africa, Asia, the Middle East, South America, North America, Europe and Oceania medicinal plants have been checked by considering the published paper. RESULTS: Based on collected data, 77 natural molecules were reported in the literature. Of which 59 were from the African region, 11 from Asia, 3 from Europe and 4 from Latin America. These active components belong to alkaloids, triterpenoids, lactone, quinoids, flavonoids, iridoids, lignans, steroids, lipids, oxygenated heterocycles, benzenoids, proteins, coumarins, phenylpropanoids and peptides. We also specified the prosperous plants with unique anti-trypanosomal activities. CONCLUSIONS: However, there is a need for further studies on the ability of the isolated compounds to ameliorate the trypanosome-induced pathological alterations and also the elucidation of their modes of actions and activities against other trypanosome species.

Pharmacotherapy consideration of thrombolytic medications in COVID-19-associated ARDS.

BACKGROUND: In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for coronavirus disease (COVID-19), was identified as the new pathogen to lead pneumonia in Wuhan, China, which has spread all over the world and developed into a pandemic. Despite the over 1 year of pandemic, due to the lack of an effective treatment plan, the morbidity and mortality of COVID-19 remains high. Efforts are underway to find the optimal management for this viral disease. MAIN BODY: SARS-CoV-2 could simultaneously affect multiple organs with variable degrees of severity, from mild to critical disease. Overproduction of pro-inflammatory mediators, exacerbated cellular and humoral immune responses, and coagulopathy such as Pulmonary Intravascular Coagulopathy (PIC) contributes to cell injuries. Considering the pathophysiology of the disease and multiple microthrombi developments in COVID-19, thrombolytic medications seem to play a role in the management of the disease. Beyond the anticoagulation, the exact role of thrombolytic medications in the management of patients with COVID-19-associated acute respiratory distress syndrome (ARDS) is not explicit. This review focuses on current progress in underlying mechanisms of COVID-19-associated pulmonary intravascular coagulopathy, the historical use of thrombolytic drugs in the management of ARDS, and pharmacotherapy considerations of thrombolytic therapy, their possible benefits, and pitfalls in COVID-19-associated ARDS. CONCLUSIONS: Inhaled or intravenous administration of thrombolytics appears to be a salvage therapy for severe ARDS associated with COVID-19 by prompt attenuation of lung injury. Considering the pathogenesis of COVID-19-related ARDS and mechanism of action of thrombolytic agents, thrombolytics appear attractive options in stable patients without contraindications.

The Virulent Hypothetical Proteins: The Potential Drug Target Involved in Bacterial Pathogenesis.

Hypothetical proteins (HPs) are non-predicted sequences that are identified only by open reading frames in sequenced genomes, but their protein products remain uncharacterized by any experimental means. The genome of every species consists of HPs that are involved in various cellular processes and signaling pathways. Annotation of HPs is important as they play a key role in disease mechanisms, drug designing, vaccine production, antibiotic production, and host adaptation. In the case of bacteria, 25-50% of the genome comprises HPs, which are involved in metabolic pathways and pathogenesis. The characterization of bacterial HPs helps to identify virulent proteins that are involved in pathogenesis. This can be done using in-silico studies, which provide sequence analogs, physiochemical properties, cellular or subcellular localization, structure and function validation, and protein-protein interactions. The most diverse types of virulent proteins are exotoxins, endotoxins, and adherent virulent factors that are encoded by virulent genes present on the chromosomal DNA of the bacteria. This review evaluates virulent HPs of pathogenic bacteria, such as Staphylococcus aureus, Chlamydia trachomatis, Fusobacterium nucleatum, and Yersinia pestis. The potential of these HPs as a drug target in bacteria-caused infectious diseases, along with the mode of action and treatment approaches, has been discussed.

Cervical and preauricular lymphadenopathies as atypical manifestations in the setting of COVID-19: a case report.

Besides the common symptoms in COVID-19, it has been thought to be a more imperative measure to identify the extraordinary manifestations of the illness, which would be more helpful to improve clinical management. In the current report, a 39-year-old woman and a 44-year-old man showed reactive cervical and preauricular lymphadenopathies, respectively, upon a range of the common symptoms of the disease. Interestingly, none of them showed the symptoms of lower respiratory tract infection as well. Notably, a herpes-like skin lesion was also observed on the right lower eyelid in one of the positive patients.