Phytochemical Agents Research Articles

Establishing capsaicin's anti-cancer intricacies in chronic myelogenous leukemia care: insights from human K562 cells

Objective: We aimed to establish capsaicin as a potent natural chemotherapeutic agent in chronic myeloid leukemia by unveiling anti-cancer mechanisms, concentrating at pro-apoptotic and anti-proliferative effects on K562 cells. Methodology: After REC approval, this research proceeded with culturing K562 cells and treatment with serial concentrations of capsaicin for calculation of subsequent 50% Inhibitory Concentration (IC50) values via MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay, expression analysis of gene, comparative analysis of relative gene fold (intrinsic biomarkers caspase-3, caspase-9) as apoptosis mediator biomarkers followed by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR). Anti-proliferative activity was confirmed via Nitric Oxide (NO) releasing Assay. Results: For K562 cells, the IC50 of capsaicin (12.1 µM) showed high gene expression of intrinsic pro-apoptotic biomarkers caspase-3 and caspase-9 with the relative gene fold of 12.1 and 13.9 respectively. Persistent peaks of NO levels confirmed the anti-proliferative potential of the compounds. Strongest growth inhibitory activity was seen at the peak time of 100-120 min. Conclusion: Capsaicin proved to be a strong pro-apoptotic and anti-proliferative phytochemical agent leading to therapeutic effects against K562 cells. Further studies would help in identifying key molecular intricacies by which capsaicin exhibits diversified anti-cancer potential. Abbreviations: CML - chronic myelogenous leukemia; NO - Nitric oxide; ROS - Reactive Oxygen Species; ROS - Reactive Oxygen Species Keywords: Capsaicin, Pro-apoptotic Effects, Anti-Cancer Mechanisms, K562 cells, Natural Chemotherapeutics Citation: Devi D, Nangdev P, Khaliq HMH, Anique M, Moqaddas A, Aziz O, Javed W. Establishing capsaicin's anti-cancer intricacies in chronic myelogenous leukemia care: insights from human K562 cells. Anaesth. pain intensive care 2024;28(5):830−835; DOI: 10.35975/apic.v28i5.2494 Received: June 26, 2024; Reviewed: August 10, 2024; Accepted: August 16, 2024

Upcycling of tea processing waste into kombucha-derived bioactive cellulosic composite for prospective wound dressing action.

The aim of the study was to utilize kombucha-derived bacterial cellulosic sheet [KBC], formed as a by-product of fermented, sugared black tea (in the presence of a symbiotic culture of bacteria and yeast), for potential wound dressing applications. KBC was functionalized using aqueous and ethanolic extracts of different phytochemical agents using two ex-situ methods- casting and impregnation. It was observed that casted KBC functionalized with ethanolic extract of Turmeric (1.2% w/w) yielded a maximum zone of inhibition (24.37 ± 0.42mm) against Pseudomonas aeruginosa. The hemocompatibility test confirmed the composite's biocompatible nature as the percentage hemocompatibility was found to be less than 5%. The MTT assay established its viability and anti-cancerous properties with Turmeric extract loaded KBC showing higher efficiency compared to Tulsi extract. FTIR analysis and SEM imaging confirmed the functionalization of cellulose sheets and the change in morphology. The contact angle analysis showed improved hydrophilic properties of the sheets for absorbing wound exudates, and the water absorption study revealed maximum absorptivity of up to 321.20 ± 6.23%. Thus, it can be concluded from the study that tea processing waste can be reused to produce a value-added product that can act as an efficient, cost-effective biomaterial for wound dressing applications.

Phytochemical Evaluation of Lepidium meyenii, Trigonella foenum-graecum, Spirulina platensis, and Tribulus arabica, and Their Potential Effect on Monosodium Glutamate Induced Male Reproductive Dysfunction in Adult Wistar Rats.

Monosodium glutamate (MSG), a sodium salt derived from glutamic acid, is widely used in commercial food products to improve taste, quality, and preservation. However, its consumption may have detrimental effects on male reproductive function. Nevertheless, plant extracts, such as Lepidium meyenii (Maca), Trigonella foenum-graecum (Fenugreek), Spirulina platensis (Spirulina), and Tribulus arabica (Tribulus), may ameliorate these adverse effects. To this effect, the phytochemical properties of Lepidium meyenii, Trigonella foenum-graecum, Spirulina platensis, and Tribulus arabica were assessed, and their potential impact on MSG-induced impairment of reproductive parameters was examined. The phytochemical composition (steroids, terpenes, phenols, flavonoids) of the plants was profiled through spectrophotometry and the antioxidant activity was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Thirty-six male Wistar rats were divided into six groups at random: a control group receiving distilled water, and five experimental groups (MSG, Maca, Fenugreek, Spirulina, and Tribulus) receiving 900 mg/kg/day of MSG dissolved in water for 45 days. Subsequently, the animals in the experimental groups were administered 500 mg/kg/day of the respective plant extract via oral gavage for an additional 35 days, while the MSG group continued to receive water only. Following the treatment period, the animals were sacrificed, and their reproductive tract organs were collected, weighed, and subjected to further analysis. Phytochemical analysis revealed the presence of diverse bioactive elements in the plant extracts, including phenolic and flavonoid compounds. Exposure to MSG negatively impacted total and progressive sperm motility, which was ameliorated by Lepidium meyenii treatment. Sperm morphology showed no significant differences among groups. Treatment of the phytochemical agents diminished histomorphometric alternations of the testicular length, germinal epithelium height, and number of cells in seminiferous tubules, which were caused by the initial administration of MSG. Testosterone and LH levels were reduced in the MSG group but improved in extract-treated groups. The study suggests Lepidium meyenii as a potential remedy for reproductive dysfunction. However, further investigation into its mechanisms and human safety and efficacy is warranted.

Biotin-modified mesoporous silica nanoparticles as a delivery system for quercetin and gallic acid for bacterial biofilm eradication

The effective management of biofilm-associated infections remains a pressing concern in clinical practice, necessitating the development of efficient eradication strategies. This study introduces biotin-modified mesoporous silica nanoparticles (MSN-Biotin) designed to facilitate the delivery of phytochemical agents, including gallic acid and quercetin, for biofilm disruption. We elucidate the synthesis, characterization, and biofilm penetration ability of MSN-Biotin towards gram-negative E. coli biofilm and gram-positive S. mutans biofilms, emphasizing their potential in anti-biofilm drug delivery. Importantly, in vitro experiments demonstrate that MSN-Biotin loaded with phytochemicals achieved significantly better penetration into E. coli and S. mutans biofilms than traditional mesoporous silica nanoparticles and better biofilm eradication ability than free phytochemical molecules. These findings underscore the promise of MSN-Biotin as a potential efficient platform for delivering antimicrobial agents. This study introduces a novel surface modification approach for the development of antibiofilm nanoparticle systems and establishes their significant potential in biofilm infection management.

Nimbolide: A Potential Phytochemical Agent in Multimodal Pancreatic Cancer Therapies.

A significant contributor to cancer-related death, pancreatic cancer (PC) has a terrible prognosis in general that has not altered over many years. Currently, it is extremely difficult to prevent disease or discover it early enough to initiate treatment. The major challenge in PC is acquired chemo-radio resistance, which makes it very difficult to manage. PC is a challenging malignancy to treat, and several major impediments significantly impact the effectiveness of its treatment. These obstacles primarily include chemoresistance, drug toxicity, and limited drug bioavailability. Phytochemicals can be used as an alternative to chemotherapeutic drugs, or they can augment the anticancer properties of the chemotherapeutic agents. Nimbolide (NL) is a prominent limonoid compound found in Azadirachta indica, and has garnered substantial attention as a phytochemical with anticancer potential. It has powerful antiproliferative effects on a variety of cancer cell lines and is effective as a chemotherapeutic in preclinical studies. The primary modes of action of NL include suppression of metastasis and angiogenesis, activation of apoptosis, anti-proliferation, and control of enzymes that metabolize carcinogens. Despite numerous pharmacodynamic (PD) investigations, NL is still in the early stages of the drug development process because no comprehensive pharmacokinetic (PK) studies or long-term toxicity studies. Preclinical PK and toxicological assessments should be conducted to establish an appropriate dosage range, ensuring the safety of NL for its application in initial human clinical trials. This review endeavors to provide a comprehensive summary of the current developmental stage of NL along with nanoparticles as a principal candidate for therapeutic purposes in PC.

Betaine Protects Mice from Cardiotoxicity Triggered by Sodium Arsenite Through Antioxidative and Anti-inflammatory Pathways.

NaAsO2 is known as a harmful pollutant all over the world, and many chronic heart diseases can be attributed to its prolonged exposure in NaAsO2-contaminated water. Therefore, considering the anti-inflammatory and antioxidant effects of betaine (BET), in this study, our team investigated the cardioprotective effects of this phytochemical agent on sodium arsenite (NaAsO2)-induced cardiotoxicity. Forty male mice were randomly divided into 4 groups: (I) Control; (II) BET (500mg/kg); (III) NaAsO2 (50ppm); and (IV) NaAsO2 + BET. NaAsO2 was given to the animals for 8weeks, but BET was given in the last two weeks. After decapitation, inflammatory factors and biochemical parameters were measured, and Western blot analyses were performed. BET decrease the activity level of alanine aspartate aminotransferase, creatine kinase MB, thiobarbituric acid reactive substances level, inflammatory factors (tumor necrosis factor-α) content, and nuclear factor kappa B expression. Furthermore, BET increased cardiac total thiol and activity levels of catalase, superoxide dismutase, and glutathione peroxidase and nuclear factor erythroid-2 expression. Hence, the administration of BET ameliorated the deleterious effects stemming from the imbalance of oxidative and antioxidant pathways and histopathological alterations observed in NaAsO2-intoxicated mice, thereby attenuating oxidative stress-induced damage and inflammation.

Human Pancreatic β Cell Regenerative Therapy: Exploring the Role of Chicoric Acid as a Phytochemical Candidate

Diabetes is a global health issue, impacting life expectancy and productivity. Pathogenesis of diabetes mellitus involves decreased functional beta cells, making beta cell replacement and regeneration a crucial area of research. However, current methods like whole pancreas transplant or stem cell-derived beta cells have limitations for diabetic patients. Exploring pharmacological approaches to stimulate regeneration of residual beta cells is valuable, as many diabetic patients retain some beta cells. Finding drugs that target and regenerate these cells effectively is a challenge, with no approved options available currently. Nature provides several therapeutic agents, and chicoric acid (CA) found in medicinal plants like Cichorium intybus, and shows potential for beta cell regeneration. Cichorium intybus possesses antioxidants, phenolics, and flavonoids, aiding its antidiabetic activity by targeting hyperglycemia, oxidative stress, inflammation, and hyperlipidemia. CA's multifaceted effects on glucose homeostasis are attributed to its involvement in various interconnected processes and pathways. This comprehensive review explores the molecular-level mechanisms through which chicoric acid facilitates beta cell regeneration, insulin release, and glucose uptake. The findings suggest that chicoric acid holds promise as a phytochemical agent for diabetes prevention and treatment. Its natural origin, antidiabetic properties, and multi-dimensional effects make it a potential candidate. Hence, further research to fully elucidate the efficacy and safety of chicoric acid for β cell regeneration as an antidiabetic agent is essential. In summary, this extensive review at the molecular level, concludes that chicoric acid is a phytochemical with great antidiabetic potential and may be indicated both as a preventive and therapeutic agent.

Pharmacokinetics behavior of four cannabidiol preparations following single oral administration in dogs.

Cannabidiol (CBD) is a natural phytochemical agent and one of the most abundant found in Cannabis sativa. It is known to exhibit pharmacological properties on various condition such as relieving-inflammation, pain, epilepsy, and anxiety effect. There has been an increasing trend globally in the use of CBD as a supplement in pets. Consequently, there are various CBD products being marketed that are specifically available for pets. Veterinarians and pet owners are concerned that following ingestion, different CBD formulations may result in a CBD level circulating in the blood that may affect the safe use and efficacy of CBD in pets. Several pharmacokinetics studies in animals have been mainly conducted with an oily form of CBD. To date, there is a lack of data regarding direct comparisons in animals among the CBD plasma kinetic profiles from an oral administration of the various preparation forms. Therefore, the current study evaluated and compared the plasma CBD levels from a single oral administration using four different CBD preparations-liquid (an oil-based form, a nanoemulsion form, or a water-soluble form) or a semi-solid form (as CBD mixed in a treat) in dogs. In total, 32 healthy, crossbreed dogs were randomly assigned into 4 groups and treated according to a 1-period, 4-treatment parallel-design. The three liquid forms were dosed at 5 mg/kg body weight, while the single semi-solid form was given at 50 mg/treat/dog. The results showed that the CBD plasma profile from the administration of a water-soluble form was comparable to that of the oil-based group. The nanoemulsion-based form tended to be rapidly absorbed and reached its peak sooner than the others. However, the CBD in all preparations reached the maximum plasma concentration within 3 h post-dose, with an average range of 92-314 μg/L. There were significant differences among certain parameters between the liquid and semi-solid forms. This was the first study to provide pharmacokinetics data regarding CBD in water soluble, nanoemulsion-based, and semi-solid forms for dogs as companion animals. The current data should facilitate the scrutiny of CBD plasma profiles based on different formulations via an oral route in dogs.

Shikonin reverses cancer-associated fibroblast-induced gemcitabine resistance in pancreatic cancer cells by suppressing monocarboxylate transporter 4-mediated reverse Warburg effect

BackgroundGemcitabine is a first-line chemotherapeutic agent for pancreatic cancer (PC); however, most patients who receive adjuvant gemcitabine rapidly develop resistance and recurrence. Cancer-associated fibroblasts (CAFs) are a crucial component of the tumor stroma that contribute to gemcitabine-resistance. There is thus an urgent need to find a novel therapeutic strategy to improve the efficacy of gemcitabine in PC cells under CAF-stimulation. PurposeTo investigate if shikonin potentiates the therapeutic effects of gemcitabine in PC cells with CAF-induced drug resistance. MethodsPC cell-stimulated fibroblasts or primary CAFs derived from PC tissue were co-cultured with PC cells to evaluate the ability of shikonin to improve the chemotherapeutic effects of gemcitabine in vitro and in vivo. Glucose uptake assay, ATP content analysis, lactate measurement, real-time PCR, immunofluorescence staining, western blot, and plasmid transfection were used to investigate the underlying mechanism. ResultsCAFs were innately resistant to gemcitabine, but shikonin suppressed the PC cell-induced transactivation and proliferation of CAFs, reversed CAF-induced resistance, and restored the therapeutic efficacy of gemcitabine in the co-culture system. In addition, CAFs underwent a reverse Warburg effect when co-cultured with PC cells, represented by enhanced aerobic glycolytic metabolism, while shikonin reduced aerobic glycolysis in CAFs by reducing their glucose uptake, ATP concentration, lactate production and secretion, and glycolytic protein expression. Regarding the mechanism underlying these sensitizing effects, shikonin suppressed monocarboxylate transporter 4 (MCT4) expression and cellular membrane translocation to inhibit aerobic glycolysis in CAFs. Overexpression of MCT4 accordingly reversed the inhibitory effects of shikonin on PC cell-induced transactivation and aerobic glycolysis in CAFs, and reduced its sensitizing effects. Furthermore, shikonin promoted the effects of gemcitabine in reducing the growth of tumors derived from PC cells and CAF co-inoculation in BALB/C mice, with no significant systemic toxicity. ConclusionThese results indicate that shikonin reduced MCT4 expression and activation, resulting in inhibition of aerobic glycolysis in CAFs and overcoming CAF-induced gemcitabine resistance in PC. Shikonin is a promising chemosensitizing phytochemical agent when used in combination with gemcitabine for PC treatment. The results suggest that disrupting the metabolic coupling between cancer cells and stromal cells might provide an attractive strategy for improving gemcitabine efficacy.

Sesamin inhibits RANKL-induced osteoclastogenesis and attenuates LPS-induced osteolysis via suppression of ERK and NF-κB signalling pathways.

Infection by bacterial products in the implant and endotoxin introduced by wear particles activate immune cells, enhance pro-inflammatory cytokines production, and ultimately promote osteoclast recruitment and activity. These factors are known to play an important role in osteolysis as well as potential targets for the treatment of osteolysis. Sesamin has been shown to have a variety of biological functions, such as inhibiting inflammation, anti-tumour and involvement in the regulation of fatty acid and cholesterol metabolism. However, the therapeutic effect of sesamin on osteolysis and its mechanism remain unclear. Present studies shown that in the condition of invitro, sesamin could inhibit osteoclastogenesis and bone resorption, as well as suppressing the expression of osteoclast-specific genes. Further studies on the mechanism suggest that the effect of sesamin on human osteoclasts was mediated by blocking the ERK and NF-κB signalling pathways. Besides, sesamin was found to be effective in treating LPS-induced osteolysis by decreasing the production of pro-inflammatory cytokines and inhibiting osteoclastogenesis invivo. Sesamin was non-toxic to heart, liver, kidney, lung and spleen. Therefore, sesamin is a promising phytochemical agent for the therapy of osteolysis-related diseases caused by inflammation and excessive osteoclast activation.

Potential Chemopreventive Effects of Dietary Combination of Phytochemicals against Cancer Development.

Cancer remains a major cause of cancer-related death worldwide. Over 70% of epithelial malignancies are sporadic and are related to lifestyle. Epidemiological studies suggest an inverse correlation between cancer incidence and fruit and vegetable intake. Numerous preclinical studies using in vitro (cell lines) and in vivo animal models of oncogenesis have reported the chemopreventive effects of dietary phytochemical agents through alterations in different biomarkers and signaling pathways. However, there is contrasting evidence from preclinical studies and clinical trials. To date, the most studied compounds include curcumin, resveratrol, isoflavones, green tea extract (epigallocatechin gallate), black raspberry powder (anthocyanins and ellagitannins), bilberry extract (anthocyanins), ginger extract (gingerol derivatives), and pomegranate extract (ellagitannins and ellagic acid). Overall, the clinical evidence of the preventive effects of dietary phytochemicals against cancer development is still weak, and the amount of these phytochemicals needed to exert chemopreventive effects largely exceeds the common dietary doses. Therefore, we propose a combination treatment of natural compounds that are used clinically for another purpose in order to obtain excess inhibitory efficacy via low-dose administration and discuss the possible reasons behind the gap between preclinical research and clinical trials.

Potency of anti-fibrotic herbs on fibrogenesis: A theoretical evaluation

BackgroundFibrosis is characterized by excessive accumulation of extracellular matrix components within organs and tissues. Anti-fibrotic treatment represents an unconquered area for drug development, with enormous potential. Herbal concoctions provide an interesting pool of potential modulators of this disease process. MethodsIn silico modeling of profibrotic genes using potential phytochemical agents will enable the identification of newer therapeutic agents. To virtually assess the efficacy of various phytochemicals as inhibitors of transforming growth factor-β (TGF-β) receptor and its downstream molecule SMAD using in silico methods, in comparison to the commercially available anti-fibrotic drug, Pirfenidone. A total of 4 phytochemicals were identified which showed stronger or similar binding affinity to TGF-β receptor type 2 molecule and SMAD molecule when compared to Pirfenidone, signifying their therapeutic potential. ResultsOur study confirmed that plumbagin and ferulic acid can be used to target TGF; rhein and curcumin can be used to target SMAD and they have anti-fibrotic potential. ConclusionsThe phytocompounds identified could be used as an anti-fibrotic drug in the treatment of fibrotic disorders. Furthermore, invitro and invivo experiments are to be carried out to validate the anti-fibrotic activity of these molecules.

Green synthesis of silver nanoparticles using aqueous leaf extract of Saussurea obvallata for efficient catalytic reduction of nitrophenol, antioxidant, and antibacterial activity

Of several noble metal nanoparticles, silver nanoparticles (AgNPs) have attracted special attention due to their distinct properties, such as favorable electrical conductivity, chemical stability, and catalytic and antibacterial activities. Green synthesis of AgNPs using plant extracts containing phytochemical agents has attracted considerable interest. This environmentally friendly approach is more biocompatible and cost-efficient and has the capability of supporting large-scale synthesis. This study developed an eco-friendly method for the preparation of AgNPs using the aqueous leaf extract of Saussurea obvallata as reducing and capping agents. Ultraviolet visible spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FTIR), Raman, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analyses were conducted to characterize the synthesized AgNPs. The morphology of AgNPs was found to be spherical with an average crystallite size of 12 nm and a maximum absorbance at 410 nm. 10 mg of AgNPs had potential to reduce 4-nitrophenol to 4-aminophenol in 16 min and exhibited strong biological activities against the Gram-negative bacteria Escherichia coli (12 mm) and Gram-positive bacteria Enterococcus faecalis (13 mm). The antioxidant activity of the synthesized AgNPs was investigated against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and exhibited up to 61.21% ± 0.02% at an AgNPs concentration of 500 μg/mL.

Andrographolide causes p53-independent HCC cell death through p62 accumulation and impaired DNA damage repair

BackgroundHepatocellular carcinoma (HCC) is a highly lethal cancer characterized by dominant driver mutations, including p53. Consequently, there is an urgent need to search for novel therapeutic agents to treat HCC. Andrographolide (Andro), a clinically available anti-inflammatory phytochemical agent, has shown inhibitory effects against various types of cancer, including HCC. However, the underlying molecular mechanisms of its action remain poorly understood. PurposeThis study aims to investigate the molecular mechanisms by which p53 and p62 collectively affect Andro-induced HCC cell death, using both in vitro and in vivo models. MethodsIn vitro cellular experiments were conducted to examine the effects of Andro on cell viability and elucidate its mechanisms of action. In vivo xenograft experiments further validated the anti-cancer effects of Andro. ResultsAndro induced dose- and time-dependent HCC cell death while sparing normal HL-7702 hepatocytes. Furthermore, Andro caused DNA damage through the generation of reactive oxygen species (ROS), a critical event leading to cell death. Notably, HCC cells expressing p53 exhibited greater resistance to Andro-induced cell death compared to p53-deficient cells, likely due to the ability of p53 to induce G2/M cell cycle arrest. Additionally, Andro-induced p62 aggregation led to the proteasomal degradation of RAD51 and 53BP1, two key proteins involved in DNA damage repair. Consequently, silencing or knocking out p62 facilitated DNA damage repair and protected HCC cells. Importantly, disruption of either p53 or p62 did not affect the expression of the other protein. These findings were further supported by the observation that xenograft tumors formed by p62-knockout HCC cells displayed increased resistance to Andro treatment. ConclusionThis study elucidates the mechanistic basis of Andro-induced HCC cell death. It provides valuable insights for repurposing Andro for the treatment of HCC, regardless of the presence of functional p53.

The Utilization of Nutraceuticals and Phytochemical Compounds to Inhibit The Interaction of Spike-protein SARS-CoV-2 Virus and ACE-2 Receptor for COVID-19 Therapy (Literature Review)

SARS-CoV-2 virus can cause Coronavirus disease 2019 (COVID-19). The interaction between spike protein and ACE2 receptor causes virus entry into the cells. The aim of this study was to review the utilization of nutraceutical and phytochemical agents to inhibit the interaction of spike protein envelope SARS-CoV-2 virus and ACE2 receptor. The data literature was retrieved from several databases such as Google scholar, Science direct, and PubMed. This study was conducted from September-October 2020. The review process was conducted based on PRISMA Guidelines.The results showed that nutraceuticals such as tuna peptides (EEAGGATAAQIEM), nisin, teicoplanin, zinc, propolis, Ganoderma lucidum, brown algae, and lectin have the potential to inhibit the interaction of spike protein SARS-CoV-2 virus and ACE2 receptor. Phytochemical compounds such as curcumin, luteolin, EGCG, hesperidin, resveratrol, saikosaponin, nicotianamine, procyanidin and the others also have the same. From this study, it can be concluded that nutraceuticals and phytochemical agents have potential benefits in COVID-19 treatment based on in silico study. However, we need further studies based on in vitro experiments and in vivo to ensure the effectivity of those nutraceutical agents.

Chondroitin/Lactoferrin-dual functionalized pterostilbene-solid lipid nanoparticles as targeted breast cancer therapy

Breast cancer remains the leading cause of cancer-associated mortality in women. Research investigating novel therapeutic approaches is thus crucial, including phytotherapeutics. Pterostilbene (PTS) is a phytochemical agent with promising efficacy against breast cancer. Poor solubility, low bioavailability and chemical instability are major drawbacks compromising PTS functionality. Herein, novel PTS-loaded solid lipid nanoparticles (PTS-SLNs) were fabricated using the ultrasonication technique. Dual-functionalization with lactoferrin (Lf) and chondroitin-sulfate (CS; CS/Lf/PTS-SLNs) was adopted as active-targeting approach. CS/Lf/PTS-SLNs demonstrated nanoparticle-size (223.42 ± 18.71 nm), low PDI (0.33 ± 0.017), acceptable zeta potential (-11.85 ± 0.07 mV) and controlled release (72.93 ± 2.93% after 24 h). In vitro studies on triple-negative MDA-MB-231 revealed prominent cytotoxicity of CS/Lf/PTS-SLNs (2.63-fold IC50 reduction), higher anti-migratory effect and cellular uptake relative to PTS-solution. The in vivo anti-tumor efficacy in an orthotopic cancer model verified the superiority of CS/Lf/PTS-SLNs; achieving 2.4-fold decrease in tumor growth compared to PTS-solution. On the molecular level, CS/Lf/PTS-SLNs enhanced suppression of VEGF, down-regulated cyclin D1 and upregulated caspase-3 and BAX, compared to PTS-solution. Also, immunohistochemical assay confirmed the higher anti-tumorigenic effect of CS/Lf/PTS-SLNs (5.87-fold decrease in Bcl-2 expression) compared to PTS-solution. Our findings highlight CS/Lf/PTS-SLNs as a promising nanoplatform for phytotherapeutic targeted-breast cancer therapy.

Fluoride-Induced Mitochondrial Dysfunction and Approaches for Its Intervention.

Fluoride is present everywhere in nature. The primary way that individuals are exposed to fluoride is by drinking water. It's interesting to note that while low fluoride levels are good for bone and tooth growth, prolonged fluoride exposure is bad for human health. Additionally, preclinical studies link oxidative stress, inflammation, and programmed cell death to fluoride toxicity. Moreover, mitochondria play a crucial role in the production of reactive oxygen species (ROS). On the other hand, little is known about fluoride's impact on mitophagy, biogenesis, and mitochondrial dynamics. These actions control the growth, composition, and organisation of mitochondria, and the purification of mitochondrial DNA helps to inhibit the production of reactive oxygen species and the release of cytochrome c, which enables cells to survive the effects of fluoride poisoning. In this review, we discuss the different pathways involved in mitochondrial toxicity and dysfunction induced by fluoride. For therapeutic approaches, we discussed different phytochemical and pharmacological agents which reduce the toxicity of fluoride via maintained by imbalanced cellular processes, mitochondrial dynamics, and scavenging the ROS.

Phytochemistry and biological activities of latex from Schubertia grandiflora Mart. (Apocynaceae)

Schubertia grandiflora is a plant species that produces latex from roots to flowers. This study aimed to evaluate the latex of S. grandiflora on qualitative phytochemical analysis and effects of quantitative biological activities. Latex was collected from logs. Phytochemical analysis of precipitation and colorimetry were carried out for several groups of phytogroups. Antifungal activity was performed on Sclerotinia sclerotiorum, Colletotrichum acutatum and C. gloeosporioides, cytotoxic activity on Artemia salina, antioxidant activity on DPPH free radical and determination of inhibition on acetylcholinesterase. The latex proved to be rich in phytochemical groups, inhibition capacity of S. sclerotiorum with 64% and for C. gloeosporioides of 30%, low rate of cytotoxicity with 25% in 1000 µg mL-1, reduction of DPPH free radical of 67% and AChE inhibition of 86%. Schubertia grandiflora latex proved to be a potential natural phytochemical agent for diverse biological activities through this study.

Therapeutic and Mechanistic Approaches of Tridax procumbens Flavonoids for the Treatment of Pyrexia: Molecular Docking

The perennial plant Tridax Procumbens is particularly intriguing, and its secondary metabolites, also known as T. procumbens flavonoids (TPFs), are well-known phytochemical agents due to their diverse medicinal uses, including their anti-inflammatory, anti-anemic, and anti-diabetic effects. The antipyretic potential of luteolin, a natural product isolated from the medicinal plant Tridax procumbens, was investigated for antipyretic action through molecular docking analyses with the target enzymes cyclooxygenase-2 (COX-2). The docking result of luteolin revealed that their docking scores was -7.24 kcal mol–1 and it can be predicted as good inhibitor of human COX2 receptor.

Design and optimization various formulations of PEGylated niosomal nanoparticles loaded with phytochemical agents: potential anti-cancer effects against human lung cancer cells.

Phytochemicals and their derivatives are good options to improve treatment efficiency in cancer patients. Artemisinin (ART) and metformin (MET) are widely used phytochemicals to treat various types of cancers. However, their application because of their dose-dependent side effects, and poor bioavailability brings several challenges. Niosome is a novel nanocarrier that is the best choice to encapsulate both lipophilic and hydrophilic drugs. In this study, we synthesized and characterized various formulations of PEGylated (polyethylene glycol) niosomal nanoparticles co-loaded with ART-MET and evaluated their anticancer effect on A549 lung cancer cells. Various formulations of PEGylated noisome were prepared by the thin-film hydration method and characterized in size, morphology, release pattern, and physicochemical structure. The cytotoxic effect of the free ART-MET and optimized PEGylated niosomal nanoparticles loaded with ART-MET on A549 cells were evaluated by MTT assay. Furthermore, the Real-time PCR (RT-PCR) technique used to evaluate apoptotic and anti-apoptotic gene expression. The size, encapsulation efficiency (EE), and polydispersity index (PDI) of the optimized nanoparticles are 256nm, 95%, and 0.202, respectively. Additionally, due to the PEGylation hydrophilic character, there is a major consideration of the high impact of PEGylation on reducing niosome size. According to the results of the MTT assay, free ART-MET and ART-MET-loaded niosomal nanoparticles showed dose-dependent toxicity and inhibits the growth of A549 lung cancer cells. Furthermore, the RT-PCR results indicated that ART-MET-loaded niosomal nanoparticles have a higher anti-proliferative effect by inhibiting anti-apoptotic and inducing apoptotic gene expression in A549 lung cancer cells. Our study revealed that the simultaneous use of ART and MET in the optimized PEGylated niosomal nanoparticles delivery system could be an appropriate approach to improve the effectiveness of lung cancer treatment.