Exploring the Therapeutic Potential of Green-fabricated CRL-AgNPs from Catharanthus roseus

Mesenchymal stromal/stem cells (MSCs) are used in many studies due to their therapeutic potential, including their differentiative ability and immunomodulatory properties. These cells perform their therapeutic functions by using various mechanisms, such as the production of anti-inflammatory cytokines, growth factors, direct cell-to-cell contact, extracellular vesicles (EVs) production, and mitochondrial transfer. However, mechanisms related to immune checkpoints (ICPs) and their effect on the immunomodulatory ability of MSCs are less discussed. The main function of ICPs is to prevent the initiation of unwanted responses and to regulate the immune system responses to maintain the homeostasis of these responses. ICPs are produced by various types of immune system regulatory cells, and defects in their expression and function may be associated with excessive responses that can ultimately lead to autoimmunity. Also, by expressing different types of ICPs and their ligands (ICPLs), tumor cells prevent the formation and durability of immune responses, which leads to tumors' immune escape. ICPs and ICPLs can be produced by MSCs and affect immune cell responses both through their secretion into the microenvironment or direct cell-to-cell interaction. Pre-treatment of MSCs in inflammatory conditions leads to an increase in their therapeutic potential. In addition to the effect that inflammatory environments have on the production of anti-inflammatory cytokines by MSCs, they can increase the expression of various types of ICPLs. In this review, we discuss different types of ICPLs and ICPs expressed by MSCs and their effect on their immunomodulatory and therapeutic potential.

Mushrooms are the healthiest, safest, most nutritious foods and are vital to human well-being. In historical contexts, religious teachings influenced the treatment of diseases, with ethnomycological knowledge suggesting that mushrooms held divine clues due to their unique appearances. The use of mushrooms was often linked to the "doctrine of signatures," where their morphological resemblance to human organs, such as the ear, kidney, and lungs, prompted researchers to theorize that products derived from mushrooms might be effective in treating health concerns. A wide variety of edible and wild mushrooms are now recognized for their bioactive compounds, which are valuable in biopharmaceuticals and dietary supplements. The compounds exhibit a range of therapeutic properties, encompassing immune enhancement, antioxidant effects, anti-inflammatory actions, antiviral capabilities, and anti-neoplastic activities. Modern science has corroborated many of these traditional insights, revealing mushrooms as sources of bioactive compounds with therapeutic potential. The intertwined filamentous mycelium of mushrooms is also attracting interest for its biocomposite uses in sustainable and environmentally friendly businesses. Biocomposite materials suitable for construction and building applications can be produced by creating a mycelial matrix or a self-forming adhesive using non-food fungal mycelia flour. This review explores the ethnomycological background, therapeutic potential, and innovative uses of mushroom mycelium in biocomposites, highlighting their role in health, wellness, and sustainable development.

The present review explains therapeutic and pharmaceutical potential of Aloe vera a well-known plant grows in semi-arid climate of tropical and subtropical regions. This article emphasizes important uses of A. vera constituents as dietary nutraceutical, medicinal, and therapeutic potential. Plant is cultivated for agricultural and medicinal and decoration purposes for indoors as a potted plant. Plant is a good depository of chemical constituents which display a very wide array of biological activities such as anticancer, antiparasitic, antidiabetic, anti-inflammatory, anti-arthritic, antiparasitic, antitumor, antioxidant, chemopreventive, hepatoprotective, and gastroprotective. Plant is used to prepare skin protective/care gels mainly for soothing, moisturizing, and wound healing. Thick watery plant sap works are added as key ingredient in many beauty products. Plant leaves are used to generate aroma, beverages, skin lotion, cosmetics, or ointments for minor burns. Plant contains vitamins, enzymes, minerals, sugars, lignin, saponins, salicylic acids, and amino acids as main ingredients. Plant is a good source of Vitamins A, C, and E, which are antioxidants. It also contains Vitamin B12, folic acid, and choline watery juicy of A. vera leaf which contains important minerals such as calcium, chromium, copper, selenium, magnesium, manganese, and potassium. Plant ingredients were found active against gingivitis, psoriasis, and used for herbal therapy in inflammatory bowel disease. A. vera contains important fatty acids mainly steroids such as cholesterol, campesterol, β-sitosterol, and lupeol. Aloin and emodin act as analgesics, antibacterials, and antivirals while lupeol shows antiseptic and analgesic properties. It also contains auxins and gibberellin hormones that help in wound healing and have anti-inflammatory action. Saponins that are the soapy substances display cleansing and antiseptic properties.

Therapeutic and pharmacological potential of Tanshinones against lung cancer: A systematic review

Cone snails, also known as marine gastropods, from Conus genus produce in their venom a diverse range of small pharmacologically active structured peptides called conotoxins. The cone snail venoms are widely unexplored arsenal of toxins with therapeutic and pharmacological potential, making them a treasure trove of ligands and peptidic drug leads. Conotoxins are small disulfide bonded peptides, which act as remarkable selective inhibitors and modulators of ion channels (calcium, sodium, potassium), nicotinic acetylcholine receptors, noradrenaline transporters, N-methyl-D-aspartate receptors, and neurotensin receptors. They are highly potent and specific against several neuronal targets making them valuable as research tools, drug leads and even therapeutics. In this review, we discuss their gene superfamily classification, nomenclature, post-translational modification, structural framework, pharmacology and medical applications of the active conopeptides. We aim to give an overview of their structure and therapeutic potential. Understanding these aspects of conopeptides will help in designing more specific peptidic analogues.

Mechanistic insights into the nutritional and therapeutic potential of Spirulina (Arthrospira) spp.: Challenges and opportunities

Soymida febrifuga, commonly known as Rohini, belongs to Meliaceae family. It is an indigenous medicinal plant, abundantly found in the forests of India and dry regions of the western Peninsula. According to the JCM Herbarium, the plant has not yet been assessed, but has been declared endangered in Madhya Pradesh. S. febrifuga has been revered since antiquity for its therapeutic and scientific significance. This article represents a comprehensive compilation of available data on S. febrifuga for the first time, drawing from classical texts, botanical floras and journal databases. It highlights the plant’s diverse therapeutic applications mentioned in Ayurveda, Siddha, Unani and traditional folk medicine. Indigenous tribes have long used it to treat conditions including malaria, diarrhoea, skin disorders and as an alternative to Cinchona bark. However, significant challenge lies in accurately identifying S. febrifuga as "Rohini" in ancient texts due to regional variations in nomenclature. Despite these traditional uses, more rigorous scientific research is needed to validate these claims. This review also examines recent studies on the phytochemical, pharmacological and therapeutic properties of S. febrifuga, alongside classical references from ancient Acharyas detailing its synonyms, properties (karmas), rasapanchak and related controversies. The plant contains flavonoids with proven antibacterial, antioxidant and hepatoprotective activities. To ensure its sustainable use, effective conservation and cultivation strategies are essential. Additionally, in-depth phytochemical investigations, pharmacological and clinical evaluations are needed to substantiate its therapeutic potential. Emerging fields such as nanotechnology, network pharmacology and materials science, combined with standardized cultivation practices, present promising avenues to enhance the therapeutic and economic potential of S. febrifuga. This review aims to bridge traditional knowledge with modern scientific approaches to unlock the full therapeutic potential of S. febrifuga, a valuable medicinal plant.

Natural products represent a therapeutic option for the treatment of inflammation- associated diseases. Flavonoids which are one of the special categories of such natural products, have previously shown promising therapeutic potential. The current review discusses the synthetic preview and anti-inflammatory potential of apigenin along with the underlying molecular mechanism in chronic human diseases especially cancer. In addition, the relevant patents on the therapeutic potential of apigenin have also been mentioned. A literature search was carried out using PubMed/Science, Google Scholar, etc. which was further expended by the different combination of keywords: apigenin, inflammation, mechanism, therapeutic potential, cancer, etc. Patent information was retrieved by searching the key terms: apigenin, inflammation, therapeutic potential from various databanks including Espacenet, Google Patents, Free Patents Online and Mendeley of WIPO, USPTO, SIPO, JPO, KIPO and EPO databases. A total of 76 references have been found relevant with the theme of the manuscript. These citations have described recent ongoing advances in the area of inflammation and cancer with respect to apigenin. Studies related to the anti-inflammatory and anticancer potential of apigenin have been explored through this review article. Moreover, the patent analysis of apigenin has further strengthened its therapeutic role. Probing into the therapeutic properties of apigenin, further adds value to this molecule in terms of its downregulation of major inflammatory and cancer-associated signaling pathways. The article would simultaneously assist the scientific community to precisely understand the role of apigenin and design novel anti-cancer therapies.

Rosa damascena, commonly known as Damask rose, has gained widespread attention for its diverse pharmacological properties and therapeutic potential. Traditionally used in herbal medicine, recent studies have highlighted its multifaceted applications, including anti-inflammatory, antioxidant, analgesic, and anxiolytic effects. This review examines the current literature on the medicinal properties of Rosa damascena, exploring its antimicrobial, anticancer, anti-HIV, cardiovascular, and anti-diabetic effects. Additionally, the plant’s role in managing mental health conditions, menstrual-related symptoms, and its potential for sustainable product development, such as eco-friendly sanitary napkins and natural cosmetics, is discussed. While evidence supports its efficacy, the mechanisms underlying these therapeutic effects remain poorly understood, and further research is needed to elucidate the plant’s bioactive compounds and their interaction with the human body. Future studies should also focus on the scalability of Rosa damascena in product development, its long-term efficacy in treating chronic conditions, and its environmental sustainability. This paper emphasizes the need for more comprehensive clinical trials, molecular studies, and eco-friendly production techniques to unlock the full therapeutic and commercial potential of Rosa damascena.

Previous research has suggested that vanishing white matter disease (VWMD) astrocytes fail to fully differentiate and respond differently to cellular stresses compared to healthy astrocytes. However, few studies have investigated potential VWMD therapeutics in monoculture patient-derived cell-based models. To investigate the impact of alterations in astrocyte expression and function in VWMD, astrocytes were differentiated from patient and control induced pluripotent stem cells and analyzed by proteomics, pathway analysis, and functional assays, in the absence and presence of stressors or potential therapeutics. Vanishing white matter disease astrocytes demonstrated significantly reduced expression of astrocyte markers and markers of inflammatory activation or cellular stress relative to control astrocytes. These alterations were identified both in the presence and absence of polyinosinic:polycytidylic acid stimuli, which is used to simulate viral infections. Pathway analysis highlighted differential signaling in multiple pathways in VWMD astrocytes, including eukaryotic initiation factor 2 (EIF2) signaling, oxidative stress, oxidative phosphorylation (OXPHOS), mitochondrial function, the unfolded protein response (UPR), phagosome regulation, autophagy, ER stress, tricarboxylic acid cycle (TCA) cycle, glycolysis, tRNA signaling, and senescence pathways. Since oxidative stress and mitochondrial function were two of the key pathways affected, we investigated whether two independent therapeutic strategies could ameliorate astrocyte dysfunction: edaravone treatment and mitochondrial transfer. Edaravone treatment reduced differential VWMD protein expression of the UPR, phagosome regulation, ubiquitination, autophagy, ER stress, senescence, and TCA cycle pathways. Meanwhile, mitochondrial transfer decreased VWMD differential expression of the UPR, glycolysis, calcium transport, phagosome formation, and ER stress pathways, while further modulating EIF2 signaling, tRNA signaling, TCA cycle, and OXPHOS pathways. Mitochondrial transfer also increased the gene and protein expression of the astrocyte marker, glial fibrillary acidic protein (GFAP) in VWMD astrocytes. This study provides further insight into the etiology of VWMD astrocytic failure and suggests edaravone and mitochondrial transfer as potential candidate VWMD therapeutics that can ameliorate disease pathways in astrocytes related to oxidative stress, mitochondrial dysfunction, and proteostasis.

Many oncolytic viruses are currently being tested as potential cancer therapeutic agents. To be effective, these viruses must replicate and propagate efficiently through the tumor mass. However, it is possible that the hypoxia that characterizes many tumors may be an obstacle to viral therapy because of its inhibition of viral replication and propagation. We, therefore, decided to test how oncolytic reovirus and its target cells respond to hypoxia. We found that reovirus infection suppresses hypoxia inducible factor (HIF)-1alpha protein levels (but not transcript abundance) in colon cancer HCT116 cells under CoCl(2) or hypoxia. Reovirus infection was able to reduce HIF-1alpha levels in both von Hippel Lindau (VHL)-/- renal carcinoma A498 and p53-/- HCT116 cells, indicating that the decrease of HIF-1alpha mediated by reovirus requires neither VHL nor p53 proteins. However, treatment with the inhibitor MG132 restored HIF-1alpha levels, suggesting that reovirus-induced HIF-1alpha decrease needs proteosomal activity. A498 VHL-/- cells with constitutive expression of HIF-1alpha were relatively resistant to reovirus-induced apoptosis when compared with A498 VHL+/+ cells. However, we found that the use of YC-1 to target HIF-1alpha promoted reovirus-induced apoptosis in A498 VHL-/- cells. Accordingly, we propose that reovirus may be used together with YC-1 as a potential therapeutic agent against chemoresistant or radioresistant tumors that are hypoxic and show increased levels of HIF-1alpha.

Alzheimer’s disease (AD) is the major dementing disorder of the elderly with four million victims of this disease in the United States. The molecular basis of AD remains unknown, but the biochemical and biophysical state of cytoskeletal proteins is reportedly altered in AD cortical neurons. No approved effective therapy for AD is available. We have used electron spin resonance (ESR) and a protein-specific spin label to investigate the interactions of three potential therapeutic agents in AD: tacrine, velnacrine, and acetylcarnitine, with cytoskeletal proteins in erythrocyte membranes. Further, we report for the first time the effects of tacrine on the physical state of membrane proteins in brain neocortex synaptosomal membranes. All three agents lead to decreased segmental motion and increased cytoskeletal protein-protein interactions in erythrocyte membranes in order of effectiveness: tacrine > velnacrine > acetylcarnitine. In addition, we have synthesized N-methylacridinium methosulfate which has a positive charge on the opposite side of the molecule relative to tacrine. This former agent gave a less pronounced diminution of the relevant ESR parameter than that caused by tacrine, implying that the orientation of the molecule with its interaction site is important in the increased cytoskeletal protein-protein interactions induced by tacrine. With synaptosomal membranes tacrine also significantly decreased segmental motion of membrane proteins. Our ESR results on erythrocyte and brain membranes suggest that in addition to their biochemical effects, these potential AD therapeutic agents function to strengthen cytoskeletal protein-protein interactions. These results are discussed with reference to possible molecular mechanisms involving cytoskeletal proteins in AD.

Prostate cancer is the second-most common malignancy of the male genitourinary system. TNF-α has attracted intense attention as a potential therapeutic agent against various cancers. However, its therapeutic application is restricted by short half life and severe toxic side-effects. In this study, we constructed a stable nanodrug, called TNF-α-derived polypeptide (P16)-conjugated, chitosan (CTS)-modified selenium nanoparticle (SC; SCP), which is composed of SC as a slow-release carrier conjugated to P16. SCP had significant inhibitory effects on multiple types of tumor cells, especially DU145 prostate cancer cells, but not on RWPE-1 normal human prostate epithelial cells. SCP could induce G0/G1 cell-cycle arrest and apoptosis in DU145 cells more effectively than could P16 and TNF-α. In DU145 xenograft tumor models, SCP exerted much stronger antitumor effects than P16 or estramustine (the clinical drug for prostate cancer) but caused fewer toxic side-effects. In addition, SCP significantly inhibited proliferation and accelerated apoptosis in DU145 xenograft tumors. Further mechanistic studies revealed that SCP exerted antitumor effects via activation of the p38 MAPK/JNK pathway, thus inducing G0/G1 cell-cycle arrest and caspase-dependent apoptosis. These findings suggest that SCP may represent a potential long-lasting therapeutic agent for human prostate cancer with fewer side effects.-Yan, Q., Chen, X., Gong, H., Qiu, P., Xiao, X., Dang, S., Hong, A., Ma, Y. Delivery of a TNF-α-derived peptide by nanoparticles enhances its antitumor activity by inducing cell-cycle arrest and caspase-dependent apoptosis.

L-carnitine is suggested as a potential therapeutic agent in metabolic encephalopathies, such as ammonia-precipitated hepatic encephalopathy (HE). In humans, ammonia is produced mainly by the metabolism of proteins and amino acids. Most of the ammonia is detoxified by the urea cycle which is located in the liver. Thus, disturbances of the urea cycle in the liver lead to higher ammonia levels in blood. In humans, hyperammonemia (HA) arises mainly from liver diseases and is in most cases associated with HE. There are currently only a few therapeutic strategies, and outcome expectations for patients with HE are poor. Lcarnitine and its acyl-derivates are suggested as potential and low-cost therapeutic agents. In animal models, L-carnitine has been shown to counteract neurotoxic effects of ammonia, increase energy metabolism and decrease mortality. A protective effect against ammoniaprecipitated HE has also been observed in cirrhotic patients. A review of the literature offers in vitro and in vivo studies, as well as human trials with promising results. This chapter provides a comprehensive summary and a summarized discussion of the literature data concerning the effects of L-carnitine, with special emphasis on hyperammonemic syndromes and HE.

The increased proliferation and activation of hepatic stellate cells (HSCs) are associated with liver fibrosis development. To date, there are no FDA-approved drugs for the treatment of liver cirrhosis. Augmentation of HSCs apoptosis is one of the resolutions for liver fibrosis. In this study, we extracted α-mangostin (1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9H-xanthen-9-one) from the fruit waste components of mangosteen pericarp. The isolated α-mangostin structure was determined and characterized with nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) and compared with those known compounds. The intracellular signaling pathway activities of α-mangostin on Transforming growth factors-beta 1 (TGF-β1) or Platelet-derived growth factor subunit B (PDGF-BB) induced HSCs activation and were analyzed via Western blot and Real-time Quantitative Polymerase Chain Reaction (Q-PCR). α-Mangostin-induced mitochondrial dysfunction and apoptosis in HSCs were measured by seahorse assay and caspase-dependent cleavage. The in vivo anti-fibrotic effect of α-mangostin was assessed by carbon tetrachloride (CCl4) treatment mouse model. The data showed that α-mangostin treatment inhibited TGF-β1-induced Smad2/3 phosphorylation and alpha-smooth muscle actin (α-SMA) expression in HSCs in a dose-dependent manner. Regarding the PDGF-BB-induced HSCs proliferation signaling pathways, α-mangostin pretreatment suppressed the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38. The activation of caspase-dependent apoptosis and dysfunction of mitochondrial respiration (such as oxygen consumption rate, ATP production, and maximal respiratory capacity) were observed in α-mangostin-treated HSCs. The CCl4-induced liver fibrosis mouse model showed that the administration of α-mangostin significantly decreased the expression of the fibrosis markers (α-SMA, collagen-a2 (col1a2), desmin and matrix metalloproteinase-2 (MMP-2)) as well as attenuated hepatic collagen deposition and liver damage. In conclusion, this study demonstrates that α-mangostin attenuates the progression of liver fibrosis through inhibiting the proliferation of HSCs and triggering apoptosis signals. Thus, α-mangostin may be used as a potential novel therapeutic agent against liver fibrosis.