Homoharringtonine: updated insights into its efficacy in hematological malignancies, diverse cancers and other biomedical applications.

HHT has emerged as a notable compound in the realm of cancer treatment, particularly for hematological malignancies. Its multifaceted pharmacological properties extend beyond traditional applications, warranting an extensive review of its mechanisms and efficacy. This review aims to synthesize comprehensive insights into the efficacy of HHT in treating hematological malignancies, diverse cancers, and other biomedical applications. It focuses on elucidating the molecular mechanisms, therapeutic potential, and broader applications of HHT. A comprehensive search for peer-reviewed papers was conducted across various academic databases, including ScienceDirect, Web of Science, Scopus, American Chemical Society, Google Scholar, PubMed/MedLine, and Wiley. The review highlights HHT's diverse mechanisms of action, ranging from its role in leukemia treatment to its emerging applications in managing other cancers and various biomedical conditions. It underscores HHT's influence on cellular processes, its efficacy in clinical settings, and its potential to alter pathological pathways. HHT demonstrates significant promise in treating various hematological malignancies and cancers, offering a multifaceted approach to disease management. Its ability to impact various physiological pathways opens new avenues for therapeutic applications. This review provides a consolidated foundation for future research and clinical applications of HHT in diverse medical fields.

Investigation of Antioxidant Activity, Myco-Chemical Content, and GC-MS Based Molecular Docking Analysis of Bioactive Chemicals from Amanita konajensis (Agaricomycetes), a Tribal Myco-Food from India.

In humans, a wide range of health disorders have been induced due to an imbalanced metabolism and an excess generation of reactive oxygen species (ROS). Different biological properties found in mushrooms seem to be the reason for their customary use as a favourite delicacy. Therefore, exploration of wild edible mushrooms as a source of various biological compounds is gaining much importance today. Amanita konajensis, one of the underutilized macrofungi popularly consumed in Eastern India, demands a systematic study of its medicinal values. The study aims to explore the myco-chemical contents of A. konajensis ethanolic extract (EtAK1) and screen their antioxidant potency through various in vitro assays. GC-MS analysis identified the chemical components of EtAK1. Further, structure-based virtual screening of the identified compounds was analysed for drug-like properties and molecular docking with the human p38 MAPK protein, a potent targeting pathway for human lung cancer. The morpho-molecular features proved the authenticity of the collected mushroom. The screening assays showed that EtAK1 was abundant in flavonoids, followed by phenolics, ß-carotene, and lycopene, and had strong antioxidant activity with EC50 values of 640-710 µg/mL. The GC-MS analyses of EtAK1 identified the occurrence of 19 bioactive compounds in the mushroom. In silico analysis revealed that anthraergostatetraenol p-chlorobenzoate, one of the compounds identified, displayed high binding affinity (ΔG = -10.6 kcal/mol) with human p38 MAPK. The outcome of this study will pave the way for the invention of myco-medicine using A. konajensis, which may lead to a novel drug for human lung cancer.

A review for cancer treatment with mushroom metabolites through targeting mitochondrial signaling pathway: In vitro and in vivo evaluations, clinical studies and future prospects for mycomedicine.

Resistance to apoptosis stands as a roadblock to the successful pharmacological execution of anticancer drug effect. A comprehensive insight into apoptotic signaling pathways and an understanding of the mechanisms of apoptosis resistance are crucial to unveil new drug targets. At this juncture, researchers are heading towards natural sources in particular, mushroom as their potential drugs leads to being the reliable source of potent bioactive compounds. Given the continuous increase in cancer cases, the potent anticancer efficacy of mushrooms has inevitably become a fascinating object to researchers due to their higher safety margin and multitarget. This review aimed to collect and summarize all the available scientific data on mushrooms from their extracts to bioactive molecules in order to suggest their anticancer attributes via a mitochondrion -mediated intrinsic signaling mechanism. Compiled data revealed that bioactive components of mushrooms including polysaccharides, sterols and terpenoids as well as extracts prepared using 15 different solvents from 53 species could be effective in the supportive treatment of 20 various cancers. The underlying therapeutic mechanisms of the studied mushrooms are explored in this review through diverse and complementary investigations: in vitro assays, pre-clinical studies and clinical randomized controlled trials. The processes mainly involved were ROS production, mitochondrial membrane dysfunction, and action of caspase 3, caspase 9, XIAP, cIAP, p53, Bax, and Bcl-2. In summary, the study provides facts pertaining to the potential beneficial effect of mushroom extracts and their active compounds against various types of cancer and is shedding light on the underlying targeted signaling pathways.

Anticancer activity and other biomedical properties of ß-sitosterol: Bridging phytochemistry and current pharmacological evidence for future translational approaches.

Sterols, including ß-sitosterol, are essential components of cellular membranes in both plant and animal cells. Despite being a major phytosterol in various plant materials, comprehensive scientific knowledge regarding the properties of ß-sitosterol and its potential applications is essential for scholarly pursuits and utilization purposes. ß-sitosterol shares similar chemical characteristics with cholesterol and exhibits several pharmacological activities without major toxicity. This study aims to bridge the gap between phytochemistry and current pharmacological evidence of ß-sitosterol, focusing on its anticancer activity and other biomedical properties. The goal is to provide a comprehensive understanding of ß-sitosterol's potential for future translational approaches. A thorough examination of the literature was conducted to gather relevant information on the biological properties of ß-sitosterol, particularly its anticancer therapeutic potential. Various databases were searched, including PubMed/MedLine, Scopus, Google Scholar, and Web of Science using appropriate keywords. Studies investigating the effects of ß-sitosterol on different types of cancer were analyzed, focusing on mechanisms of action, pharmacological screening, and chemosensitizing properties. Modern pharmacological screening studies have revealed the potential anticancer therapeutic properties of ß-sitosterol against various types of cancer, including leukemia, lung, stomach, breast, colon, ovarian, and prostate cancer. ß-sitosterol has demonstrated chemosensitizing effects on cancer cells, interfering with multiple cell signaling pathways involved in proliferation, cell cycle arrest, apoptosis, survival, metastasis invasion, angiogenesis, and inflammation. Structural derivatives of ß-sitosterol have also shown anti-cancer effects. However, research in the field of drug delivery and the detailed mode of action of ß-sitosterol-mediated anticancer activities remains limited. ß-sitosterol, as a non-toxic compound with significant pharmacological potential, exhibits promising anticancer effects against various cancer types. Despite being relatively less potent than conventional cancer chemotherapeutics, ß-sitosterol holds potential as a safe and effective nutraceutical against cancer. Further comprehensive studies are recommended to explore the biological properties of ß-sitosterol, including its mode of action, and develop novel formulations for its potential use in cancer treatment. This review provides a foundation for future investigations and highlights the need for further research on ß-sitosterol as a potent superfood in combating cancer.

A natural derivative from ethnomedicinal mushroom potentiates apoptosis, autophagy and attenuates cell migration, via fine tuning the Akt signaling in human lung adenocarcinoma cells (A549).

Although comprehensive exertions have been made in late decades for treating advanced lung cancer with inclusive therapies but efficient anti-lung cancer therapeutics are statically inadequate in the clinics. Hence, compelling novel anti-lung cancer drugs are considerably desired. This backdrop enticed us to unveil anticancer efficacy of astrakurkurol, derivative of wild edible mushroom against lung cancer, whose effects have not yet been described. Mechanistic analysis disclosed that sensitizing effect of astrakurkurol is due to cell cycle arrest at G0/G1 phase, increased level of Fas, FADD, decreased ratio of Bax/Bcl-2, and increased cleaved form of caspase 9, 8, and 3. Apart from the induction of apoptosis, it was demonstrated for the first time that astrakurkurol induced an autophagic response as evidenced by the development of acidic vesicular organelles (AVOs) with up-regulation of beclin-1, Atg7, and downregulated p62. Apoptosis and autophagy can be sparked by the same stimuli, which was as evident from the astrakurkurol-induced inactivation of PI3K/AKT signaling. The thorough scanning of the mechanism of crosstalk between apoptosis and autophagy is requisite for prosperous anticancer remedy. Triterpenoid has evidently intensified cytotoxicity, induced apoptosis and autophagy on A549 cells. Besides astrakurkurol could also curb migration and regress the size of tumor in ex ovo xenograft model. All these findings put forth astrakurkurol as a convincing novel anti-cancer agent, for scrutinizing the lung cancer therapies and as a robust contender for future in vitro and in vivo analysis.

Anti-cancer effect of astrakurkurol from a folklore tribal mushroom on human hepatocellular carcinoma cells via mediating cell cycle inhibition, apoptosis, and migration.

Astraeus hygrometricus extensively been utilized by tribal people for long time. A triterpene, astrakurkurol has been isolated from A. hygrometricus but anticancer effect of this novel triterpene has imperceptibly been investigated. Motive of this research was to scrutinize its underlying apoptotic mechanism in HepG2 cells. Cytotoxicity studies demonstrated a selective effect of astrakurkurol with towering influence in HepG2 than Thle2 cells. The exposure of these triterpene-induced marked apoptotic morphological changes enhanced the rate of cell apoptosis and arrest cell cycle at G0/G1. Furthermore, these results are aided by decline in the expression of Bcl-2, Bcl-xL with an increase in the expression of p53, Bax, Fas, FADD together with the activation of caspase cascade. Astrakurkurol also displayed a remarkable anti-migratory capacity at a lower concentration. Altogether, studies explained anti-proliferative, pro-apoptotic, and anti-migratory efficacy of astrakurkurol on HepG2, composing a gripping challenge in the advancement of novel treatments against hepatocellular carcinoma. PRACTICAL APPLICATIONS: Mushrooms, the minuscule pharmaceutical factory, bear hundreds of novel elements with incredible biological attributes. Triterpenoids from mushrooms has been proven to bear potentials of curing cancer. This study highlights the cytotoxic and anti-migratory effects of novel triterpene in vitro in HepG2 cell, an HCC cell line. Astrakurkurol mediated cell death via both extrinsic and intrinsic apoptotic signaling. Utilization of astrakurkurol will provide a non-toxic substitute of chemotherapy and also uplift the value of forsaken taxon, Astraeus and boost the rural acceptance.

Azide-mediated unusual in situ transformation of Mannich base to Schiff-Mannich base and isolation of their Cu(II) complexes: crystal structure, theoretical inspection and anticancer activities.

A new "end-off" compartmental Mannich ligand (HL1) namely 3-((bis(2-methoxyethyl)amino)methyl)-5-bromo-2-hydroxybenzaldehyde containing two methoxyethyl pendant arms and one-CHO functionality has been synthesized through conventional C-C and C-N coupling reactions. On treatment with Cu(ClO4)2, HL1 yields a dinuclear µ-phenolatocopper(II) complex having the molecular formula [Cu2(L1)2](ClO4)2(H2O)1.5 (1). Surprisingly, the ligand HL1 is radically transformed into a new asymmetric Schiff-Mannich base ligand (HLF) in the presence of NaN3 and Cu(ClO4)2 forming a unique dinuclear centro-symmetric Cu(II) complex [Cu(LF)]2 (2) as evident from single-crystal X-ray diffraction (SCXRD) analysis. A probable mechanistic rationalization has been proposed on the basis of theoretical calculations, which suggests systematic fragmentation of HL1 in the presence of azide residue and re-condensation of the fragmented units to yield the final Cu-HLF complex (2). SCXRD analysis portrays a large inter-metallic distance in complex 2 in comparison with complex 1 (5.493 vs. 2.989 Å, respectively) along with other distinct structural features. After physicochemical characterization both the complexes have been exploited to evaluate their possible anticancer proficiency on lung adenocarcinoma cell line (A549). Complex 1 distinctly impeded the proliferation of lung adenocarcinoma cells in a dose-dependent manner more efficiently than complex 2. Due to the behavior of complex 1 as potential therapeutics, cellular transformations of A549 cells have been systematically investigated. As evidenced from various in vitro experiments, the cell death mechanism triggered by complex 1 turned out to be apoptosis, as indicated by the DNA fragmentation, chromatin condensation, membrane blebbing and imbalanced cell cycle distribution as well as retard migration in A549 cells.

Prospecting medicinal properties of Lion's mane mushroom.

Hericium erinaceus (Bull.) Persoon, a popular medicinal edible mushroom, owns a long history of usage in traditional Chinese medicine and also in other oriental countries. Along with this, its several bioactive compounds have been evolved into food supplements. Meanwhile, this present investigation aimed at extracting bioactive components from fruiting bodies of H. erinaceus using two different solvents and evaluating its in vitro antioxidant, antimicrobial, and antiproliferative efficacy. Chemical analysis showed extracts were rich in phenol, flavonoids, and ascorbic acids while lesser amount of carotenoids were also detected in these extracts. Both extracts were able to scavenge 1,1-diphenyl-2-picrylhydrazyl (~76%) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) radicals (~81%) and also showed chelating activity (~73.05%). The ethanolic extract exhibited the highest antioxidant activity (total antioxidant capacity 2.17 µg ascorbic acid equivalent/mg of extract) whereas methanolic extract showed moderate capacity (total antioxidant capacity 1.42 µg ascorbic acid equivalent/mg of extract). All extracts displayed antibacterial activity against both Gram-positive and Gram-negative bacteria as well (minimum inhibition concentration 1,575-2,750 µg/ml) although methanolic extract showed some selectivity towards bacterial strains. Apart from these, ethanolic fraction has found to exhibit potent cytotoxicity (IC50 403.12 µg/ml) towards lung adenocarcinoma cells. These studies thus provide the reference data that could support this mushroom as an easily accessible source of natural bioactive components. PRACTICAL APPLICATIONS: Mushroom extracts have long been traditionally used as miracle medicine to treat an extensive range of ailments. These findings indicate the potential benefits of the Hericium erinaceus (Bull.) Persoon extracts for the development of multi-target therapeutics as well as extraction with appropriate solvents also provide leads for the isolation of various principle compounds. The extracts thus could be used to treat oxidative stress-related disorders as they are found to contain antioxidant compounds like phenols and others and also they possessed good antimicrobial and anticancer activity.

Characterization and Inception of a Triterpenoid Astrakurkurol, as a Cytotoxic Molecule on Human Hepatocellular Carcinoma Cells, Hep3B.

Mushrooms are customary influential sources of pharmaceutically active metabolites. Usually lanostane-type triterpenoids from mushrooms had prospective for cancer disease treatments. Recently, a triterpenoid, astrakurkurol obtained from the fresh basidiocarps of the edible mushroom Astraeus hygrometricus, drew attention as a new cytotoxic therapeutic. The structural stability of this triterpenoid had been established with the amalgamation of density functional theory (DFT) calculations and study of single-crystal X-ray diffraction. To successfully manifest astrakurkurol as a potent cytotoxic therapeutics, a wide apprehension on the molecular and cellular mechanisms underlying their action is prerequisite. On this account, our study was directed to scrutinize the influence of this triterpenoid on human hepatocellular cancer cell model Hep3B. Encapsulating all experimental facts revealed that astrakurkurol had significantly decreased cell viability in a concentration-dependent manner. This effect was unveiled to be apoptosis, documented by DNA fragmentation, chromatin condensation, nuclear shrinkage, membrane blebing, and imbalance of cell cycle distribution. Astrakurkurol persuaded the expression of death receptor associated proteins (Fas), which triggered caspase-8 activation following tBid cleavage. Moreover, tBid mediated ROS generation, which triggered mitochondrial dysfunction and activated the mitochondrial apoptotic events. Astrakurkurol cytotoxicity was based on caspase-8-mediated intrinsic apoptotic pathway and was associated with inhibition at Akt and NF-κB pathway. Astrakurkurol had also inhibited the migration of Hep3B cells, indicating its antimigratory potential. These findings led us to introduce astrakurkurol as a feasible and natural source for a safer cytotoxic drug against hepatocellular carcinoma.

Microanatomical and Physicochemical Characterization and Antioxidative Activity of Methanolic Extract of Oudemansiella canarii (Jungh.) Höhn.

OBJECTIVES: Oudemansiella canarii is an edible mushroom highly appreciated throughout the world due to its being a gastronomic delicacy. To date, no extensive work has been reported on the pharmacological or antioxidative aspects of this macrofungus. The present study focuses on the micromorphological features, confirmation of its identity based on molecular sequence (nrITS rDNA) data, and determination of its physicochemical parameters such as organoleptic features and fluorescent behavior. MATERIALS AND METHODS: Collected basidiocarps were powdered and used for microscopic and organoleptic evaluation. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method, total antioxidant activity methods, and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay were used for evaluating the antioxidant capacities of the methanolic extract. High-performance liquid chromatography (HPLC) analysis profile was also recorded to analyze the phenolic fingerprint. RESULTS: The DPPH radical scavenging activity was determined with an EC50 value of 0.912 µg, total antioxidant activity was found to be 15.33 µg ascorbic acid equivalent/mg of extract, and the ABTS assay revealed 12.91 µm TE/mg of extract antioxidant activity. The HPLC chromatogram revealed the presence of 12 peaks. Several parameters were tested for the determination of chemical composition, revealing the existence of major bioactive components in the extract in the following order: phenol>flavonoid>ascorbic acid>ß-carotene~lycopene. CONCLUSION: The present work suggests that O. canarii may be considered a novel prospect as a functional food and antioxidant supplement.

Expansive arterial remodeling is associated with increased neointimal macrophage foam cell content: the murine model of macrophage-rich carotid artery lesions.

BACKGROUND: Recent observations associate plaque instability with expansive arterial remodeling, suggesting a common driving mechanism. METHODS AND RESULTS: To demonstrate that macrophages, a characteristic of vulnerable plaques, also assist in expansive remodeling, we compared carotid artery remodeling due to formation of experimental macrophage-rich and macrophage-poor lesions in the flow cessation model in hypercholesterolemic apolipoprotein E knockout (ApoE KO) and wild type (WT) mice. After ligation, macrophages started to rapidly accumulate in ApoE KO but not in WT carotid artery lesions. Macrophage-rich ApoE KO intimal lesions grew fast, typically occluding within 14 days, despite a tripling of the vessel area. Outward remodeling of macrophage-rich ApoE KO arteries positively correlated with macrophage area (r2=0.600, P<0.001). To investigate potential mechanisms of macrophage-enabled expansive remodeling, we compared levels of matrix metalloproteinases in homogenates of macrophage-rich and macrophage-poor carotid arteries. Gelatinolytic activity of macrophage-rich lesions increased faster and reached maximal levels several fold higher than in the macrophage-poor WT lesions. CONCLUSIONS: Our results suggest that macrophages facilitate expansive arterial remodeling through increased matrix degradation by matrix metalloproteinases. This initially favorable remodeling action may eventually increase the vulnerability of macrophage-rich atherosclerotic plaques.