Natural Products Research Articles

Dietary Natural Flavonoids: Intervention for MAO-B Against Parkinson's Disease.

Parkinson's disease (PD) stands as the second most common neurological disorder after Alzheimer's disease, primarily affecting the elderly population and significantly compromising their quality of life. The precise etiology of PD remains elusive, but recent research has shed light on potential factors, including the formation of α-synuclein aggregates, oxidative stress, neurotransmitter imbalances, and dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc) region of the brain, culminating in motor symptoms such as bradykinesia, akinesia, tremors, and rigidity. Monoamine oxidase (MAO) is an essential enzyme, comprising two isoforms, MAO-A and MAO-B, responsible for the oxidation of monoamines such as dopamine. Increased MAO-B activity is responsible for decreased dopamine levels in the SNpc region of mid brain which is remarkably associated with the pathogenesis of PD-like manifestations. Inhibitors of MAO-B enhance striatal neuronal responses to dopamine, making them valuable in treating PD, which involves dopamine deficiency. Clinically approved MAO-B inhibitors such as selegiline, L-deprenyl, pargyline, and rasagiline are employed in the management of neurodegenerative conditions associated with PD. Current therapeutic interventions including MAO-B inhibitors for PD predominantly aim to alleviate these motor symptoms but often come with a host of side effects that can be particularly challenging for the patients. While effective, they have limitations, prompting a search for alternative treatments, there is a growing interest in exploring natural products notably flavonoids as potential sources of novel MAO-B inhibitors. In line with that, the present review focuses on natural flavonoids of plant origin that hold promise as potential candidates for the development of novel MAO-B inhibitors. The discussion encompasses both invitro and invivo studies, shedding light on their potential therapeutic applications. Furthermore, this review underscores the significance of exploring natural products as valuable reservoirs of MAO-B inhibitors, offering new avenues for drug development and addressing the pressing need for improved treatments in PD-like pathological conditions. The authors of this review majorly explore the neuroprotective potential of natural flavonoids exhibiting notable MAO-B inhibitory activity and additionally multi-targeted approaches in the treatment of PD with clinical evidence and challenges faced in current therapeutic approaches.

Evaluating the quality, physicochemical properties, and biological activities of Centauri® honey from Turkey

Honey, a natural production of honeybees, underscores Turkey's prominence as one of the world's largest honey producers. The country's diverse flora fosters optimal conditions for beekeeping, resulting in the production of exceptional-quality honey. Centauri® Honey is uniquely sourced from remote alpine regions in Turkey, characterized by bees that inhabit isolated caves with access to medicinal endemic flowers year-round, promoting a unique and pristine production environment. This study evaluates the quality, physicochemical properties, nutritional parameters, and biological activities of five types of Centauri® Honey. The in vitro studies highlighted significant nitric oxide inhibition in Centauri® Cave Honey, suggesting it is a promising candidate for further research and potential therapeutic applications, especially in enhancing immune responses by reducing the inflammatory response. This study confirms that Centauri® honey not only adheres to the rigorous standards of the Codex Alimentarius but also offers substantial health benefits, advocating for continued research into its medicinal applications.

Different impacts of natural and anthropogenic factors on dissolved organic matter chemistry in coastal rivers: Implications for water management

The chemical composition of dissolved organic matter (DOM) exerts significant influence on aquatic energy dynamics, pollutant transportation, and carbon storage, thereby playing pivotal roles in the local water quality and regional-global biogeochemical cycling. However, the effects of natural climate change and local human activities on watershed characteristics and in-river processes have led to uncertainties regarding their contributions to DOM chemistry in coastal rivers, creating challenges for effective water management and the study of organic matter cycling. In this investigation, we employed a combination of stable isotopic analysis, optical techniques, and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) to elucidate the sources, optical properties, and molecular composition of DOM in three South China coastal rivers. Our results suggest that terrestrial DOM entering the three rivers through natural or anthropogenic pathways is gradually diluted by in situ primary production as it moves downstream, ultimately being influenced by seawater intrusion near the estuary. Additionally, terrestrial processes influenced by temperature likely govern DOC concentration, while seawater intrusion promotes the natural production of S-containing organic compounds. In contrast, human-altered landcover significantly impacts DOM molecular composition. Increased water areas lead to the enrichment of lignins with high disinfection byproduct formation potential, and agricultural residue burning appears to be the dominant source of pyrogenic DOM in these coastal rivers. Our distinct results suggest that the development of specific water management plans that consider the combined effects of temperature, seawater intrusion, landcover changes, and agricultural practices will be essential to ensure sustainable water resource.

Natural products‐based antiangiogenic agents: New frontiers in cancer therapy

AbstractAngiogenesis, vital for tumor growth and metastasis, is a promising target in cancer therapy. Natural compounds offer potential as antiangiogenic agents with reduced toxicity. This review provides a comprehensive overview of natural product‐based antiangiogenic therapies, focusing on molecular mechanisms and therapeutic potential. A systematic search identified relevant articles from 2019 to 2023. Various natural compounds, including polyphenols, terpenes, alkaloids, cannabinoids, omega‐3 fatty acids, polysaccharides, proteins, and carotenoids, were investigated for their antiangiogenic properties. Challenges such as dose standardization, routes of administration, and potential side effects remain. Further studies, including in‐depth animal models and human epidemiological studies, must elucidate clinical efficacy and safety. Synergistic effects with current antiangiogenic therapies, such as bevacizumab and tyrosine kinase inhibitors, should be explored. Additionally, the potential hormone‐dependent effects of compounds like genistein highlight the need for safety evaluation. In conclusion, natural products hold promise as adjunctive therapies to conventional antineoplastic drugs in modulating angiogenesis in cancer. However, robust clinical trials are needed to validate preclinical findings and ensure safety and efficacy.

AKR1C1 interacts with STAT3 to increase intracellular glutathione and confers resistance to oxaliplatin in colorectal cancer

Oxaliplatin (OXA), a platinum-based chemotherapeutic agent, remains a mainstay in first-line treatments for advanced colorectal cancer (CRC). However, the eventual development of OXA resistance represents a significant clinical challenge. In the present study, we demonstrate that the aldo-keto reductase 1C1 (AKR1C1) is overexpressed in CRC cells upon acquisition of OXA resistance, evident in OXA-resistant CRC cell lines. We employed genetic silencing and pharmacological inhibition strategies to establish that suppression of AKR1C1 restores OXA sensitivity. Mechanistically, AKR1C1 interacts with and activates the transcription factor STAT3, which upregulates the glutamate transporter EAAT3, thereby elevating intracellular glutathione levels and conferring OXA resistance. Alantolactone, a potent natural product inhibitor of AKR1C1, effectively reverses this chemoresistance, restricting the growth of OXA-resistant CRC cells both in vitro and in vivo. Our findings uncover a critical AKR1C1-dependent mechanism behind OXA resistance and propose a promising combinatorial therapeutic strategy to overcome this resistance in CRC.

Influence of extraction solvents on the chemical constituents and biological activities of Astragalus aduncusfrom Turkey flora: In vitro and in silico insights.

The n-hexane, ethyl acetate, ethanol, ethanol/water (70% ethanol), and water extracts of Astragalus aduncus aerial parts were investigated for their antioxidant potential, enzyme inhibition activity (anti-acetylcholinesterase [AChE], anti-butyrylcholinesterase [BChE],antityrosinase, antiamylase, and antiglucosidase) and antiproliferative effect (against colon adenocarcinoma cell line[HT-29], gastric cancer cell line[HGC-27], prostate carcinoma cell line[DU-145], breast adenocarcinoma cell line[MDA-MB-231],and cervix adenocarcinoma cell line [HeLa]). In addition, the phytochemical profile of the extracts was evaluated using validated spectrophotometric and high-pressure liquid chromatography-electrospray ionization/tandem mass spectroscopymethods. Generally, the 70% ethanol extract demonstrated the strongest antioxidant properties, and it was the richest source of total phenolic constituents. Our findings indicated that the ethyl acetate extract was the most potent BChE inhibitor (11.44 mg galantamine equivalents [GALAE]/g) followed by the ethanol extract (8.51 mg GALAE/g), while the ethanol extract was the most promising AChE inhibitor (3.42 mg GALAE/g) followed by the ethanol/water extract (3.17 mg GALAE/g).Excellent tyrosinase inhibitory activity (66.25 mg kojic acid equivalent/g) was observed in ethanol/water extracts of the aerial part of A. aduncus. Тhese results showed that the most cytotoxic effects were exhibited by the ethyl acetate extract against HGC-27 cells (IC50: 36.76 µg/mL), the ethanol extract against HT-29 cells (IC50: 30.79 µg/mL), and the water extract against DU-145 cells (IC50: 37.01 µg/mL). A strong correlation was observed between the highest total flavonoid content and the highest content of individual compounds in the ethanol extract, including rutin, hyperoside, isoquercitrin, delphinidin-3,5-diglucoside (delphinidin-3,5-O-diglucoside), and kaempferol-3-glucoside (kaempferol-3-O-glucoside). In the present study, the A. aduncus plant was considered a new source of antioxidants, enzyme inhibitors, and anticancer agents and could be used as a future health-benefit natural product.

Exploring Brominated Aromatic Butenolides from Aspergillus terreus EGF7-0-1 with Their Antifungal Activities.

Fungal diseases could severely harm agricultural productions. To develop new antifungal agents, based on the Global Natural Products Social Molecular Networking, typical bromine isotope peak ratios, and ultraviolet absorptions, cultivation of the soft coral-derived endophytic fungi Aspergillus terreus EGF7-0-1 with NaBr led to the targeted isolation of 14 new brominated aromatic butenolides (1-14) and six known analogues (15-20). Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1-14 exhibited wildly antifungal activities (against Colletotrichum gloeosporioides, Pestalotiopsis microspora, Fusarium oxysporum f. sp. cubense, Botrytis cinerea, and Diaporthe phoenicicola). The bioassay results showed that compounds 1-14 exhibited excellent antifungal activities against C. gloeosporioides, with concentration for 50% of maximal effect (EC50) values from 2.72 to 130.41 nM. The mechanistic study suggests that compound 1 may disrupt nutrient signaling pathways by reducing the levels of metabolites, such as carbohydrates, lipids, and amino acids, leading to an increase in low-density granules and a decrease in high-density granules in the cytoplasm, accompanied by numerous vacuoles, thereby inhibiting the growth of C. gloeosporioides. Monobrominated γ-butenolide 1 may be expected to exploit a novel agriculturally antifungal leading drug. Meanwhile, compound M1 has conformed antifugual activities against C. gloeosporioides by papayas in vivo.

New Emerging Aspect of Herbal Extracts for the Treatment of Osteoporosis: Overview.

As the global population ages, osteoporosis is becoming a more common silent disease. Osteoporosis is characterized by decreased bone quality and strength, which increases the risk of fragility fractures in the elderly. According to estimates, 50% of women eventually suffer from an osteoporotic fracture. Due to increasing disability, more frequent hospital hospitalizations, and most critically, fragility fractures have been linked to a reduced quality of life. Osteoporotic fractures have been linked to an increased mortality risk; and must be considered in awareness as a serious health concern. There are anti-osteoporotic medications available that improve bone quality. Considering the availability of various treatment options, still there are a lot of underserved needs in the treatment of fractures and osteoporosis. For example, the application of natural products and herbal resources for fracture healing, because of the androgen-like and antioxidant characteristics of the plants, they can play a crucial for accelerating the repair of bone fractures. In this article, we'll discuss the herbal remedies that are essential for treating osteoporosis (bone disease).

Identification of a Novel 10-hydroxyevodiamine Prodrug as a Potent Topoisomerase Inhibitor with Improved Aqueous Solubility for Treatment of Hepatocellular Carcinoma

Natural product evodiamine (Evo) and its synthetic derivatives represent an attractive dual Topo 1/2 inhibitors with broad-spectrum antitumor efficacy. However, the clinical applications of these compounds have been impeded by their poor aqueous solubility. Herein, a series of water-soluble 10-substituted-N(14)-phenylevodiamine derivatives were designed and synthesized. The most potent compound 45 featuring a quaternary ammonium salt fragment achieved robust aqueous solubility and nanomolar potency against a panel of human hepatoma cell lines Huh7, HepG2, SK-Hep-1, SMMC-7721, and SMMC-7721/DOX (doxorubicin-resistant cell). Further studies revealed that 45 could inhibit Topo 1 and Topo 2, induce apoptosis, arrest the cell cycle at the G2/M stage and inhibit the migration and invasion. Compound 45 exhibited potent antitumor activity (TGI = 51.1%, 10 mg/kg) in the Huh7 xenograft model with acceptable safety profile. In addition, a 21-day long-term dose toxicity study confirmed that the maximum tolerated dose of compound 45 was 20 mg/kg. Overall, this study presented a promising Evo-derived candidate for the treatment of hepatocellular carcinoma.

Carbon-Dots-Mediated Improvement of Antimicrobial Activity of Natural Products.

The development of new microbicidal compounds has become a top priority due to the emergence and spread of drug-resistant pathogenic microbes. In this study, blue-emitting and positively charged carbon dots (CDs), called Du-CDs, were fabricated for the first time utilizing the natural product extract of endophyte Diaporthe unshiuensis YSP3 as raw material through a one-step solvothermal method, which possessed varied functional groups including amino, carboxyl, hydroxyl, and sulfite groups. Interestingly, Du-CDs exhibited notably enhanced antimicrobial activities toward both bacteria and fungi as compared to the natural product extract of YSP3, with low minimum inhibitory concentrations. Moreover, Du-CDs significantly inhibited the formation of biofilms. Du-CDs bound with the microbial cell surface via electronic interaction or hydrophobic interaction entered the microbial cells and were distributed fully inside the cells. Du-CDs caused cell membrane damage and/or cell division cycle interruption, resulting in microbial cell death. Moreover, Du-CDs exhibited an improved antimicrobial effect and accelerated wound healing ability with good biocompatibility in the mouse model. Overall, we demonstrate that the formation of CDs from fungal natural products presents a promising and potential means to develop novel antimicrobial agents with great fluorescence, improved microbiocidal effect and wound healing capacity, and good biosafety for combating microbial infections.

Phytochemicals, Two New Sulphur Glycosides and Two New Natural Products, from Shepherd’s Purse Seed and Their Activities

Two new sulfur glycosides, bursapastoris A–B (3–4), were extracted and isolated from shepherd’s purse seed, along with two new natural products, 11-(methylsulfinyl)undecanoic acid (2) and 10-(methylsulfinyl)decanoic acid (1). Their structures were determined though infrared spectroscopy, one-dimensional nuclear magnetic resonance (1H and 13C), and electrospray ionization mass spectrometry. Additionally, the structures of 3–4 were further identified by two-dimensional nuclear magnetic resonance (HMBC, HSQC, 1H-1H COSY, and NOESY). Compounds 1–4 showed relatively favorable docking to NF-κB. Unfortunately, we only discovered that compound 1–4 had weak anti-radiation activity at present. Therefore, further research regarding the biological activity of these organosulfur compounds is required at a later stage.

Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr‐Catalyzed Dimerization

A concise synthetic strategy utilizing a Zr‐catalyst for the construction of cyctetryptomycin A and B is herein reported. Cyctetryptomycin A and B are recently isolated, complex tetrameric natural products for which total synthesis has not been previously reported. This study presents a practical approach for the construction of two consecutive quaternary carbon centers via a Zr‐catalyst. Furthermore, the first total synthesis of cyctetryptomycin A and B was achieved by this Zr‐catalyzed radical coupling. The radical dimerization reaction mediated by the Zr‐catalyst required dppe as an indispensable additive. Through both experimental and theoretical investigations into the mechanism of this Zr‐catalyzed reaction, the specific role of dppe was elucidated. In addition, the synthetic approach was extended to enable the practical synthesis of other dimeric natural products, including tetratryptomycin A, dibrevianamide F, and ditryptophenaline. Finally, the synthetic mechanism of cyctetryptomycin A and B, through the oxidative macrocyclization of tetratryptomycin A by CttpC, was newly elucidated by both experimental and docking simulations.

Jack bean urease inhibition by different root fractions of Cleome gynandra L – Kinetic mechanism and computational molecular modelling

Natural products with urease inhibiting potentialities would be valuable for enhancing nitrogen fertilizer formulations and developing new therapeutics against infectious diseases. Main focus of this research was to assess the inhibitory impact of various parts of Cleome gynandra (Cleomaceae) on jack bean urease activity, identify the responsible compounds, and ascertain their mode of enzyme inhibition and interactions with urease enzyme. Urease inhibitory potentiality of different plant parts of C. gynandra was determined using the phenol-hypochlorite method and mode of enzyme inhibition by Lineweaver-Burk kinetic analysis. LC-HRMS was carried out to identify the compounds of the active fractions. Molecular docking and simulations were executed to find out the binding affinity and interaction pattern of the isolated compounds at the active site of urease enzyme and to verify stability of protein-inhibitor complexes. The root of C. gynandra exhibited highest urease inhibitory potentiality with IC50 value of 1.529 mg/ml compared with leaf and stem. Among the different root fractions, water fraction revealed maximum anti-urease activity with IC50 values of 1.477 mg/ml followed by methanol (1.655 mg/ml) and acetone fractions (1.955 mg/ml). Inhibition kinetics indicated that these fractions were strong inhibitors of urease and exhibited a non-competitive mode of inhibition with Ki values of 184.911 µg/ml, 147.34 µg/ml, and 233.75 µg/ml respectively at 1000 mg/L concentration. LC-HRMS analysis confirmed the occurrence of glucocapparin, fluticasone propionate and lauryl hydrogen sulfate etc. in water fraction. Molecular modelling and simulation study suggested strong and stable interactions between the specified compounds of water fraction and active site of urease. Hence, the water fraction of C. gynandra roots represent a valuable source of natural urease inhibitors, for possible therapeutic applications and sustainable agricultural practices.

Concise Synthesis of Cyctetryptomycin A and B Enabled by Zr-Catalyzed Dimerization.

A concise synthetic strategy utilizing a Zr-catalyst for the construction of cyctetryptomycin A and B is herein reported. Cyctetryptomycin A and B are recently isolated, complex tetrameric natural products for which total synthesis has not been previously reported. This study presents a practical approach for the construction of two consecutive quaternary carbon centers via a Zr-catalyst. Furthermore, the first total synthesis of cyctetryptomycin A and B was achieved by this Zr-catalyzed radical coupling. The radical dimerization reaction mediated by the Zr-catalyst required dppe as an indispensable additive. Through both experimental and theoretical investigations into the mechanism of this Zr-catalyzed reaction, the specific role of dppe was elucidated. In addition, the synthetic approach was extended to enable the practical synthesis of other dimeric natural products, including tetratryptomycin A, dibrevianamide F, and ditryptophenaline. Finally, the synthetic mechanism of cyctetryptomycin A and B, through the oxidative macrocyclization of tetratryptomycin A by CttpC, was newly elucidated by both experimental and docking simulations.

Life Cycle Assessment of Natural Gas Production in Java Sea-East Java Province, Indonesia

Energy products including natural gas play a very important role in the context of global economic, industrial, and infrastructure development. However, it is undeniable that the production process from raw material extraction to ready-to-use products has an impact on the environment. This study was conducted to evaluate the environmental impact of natural gas production in the Kepodang field, East Java Province, Indonesia. The next objective is to analyze the magnitude and significance of the impact or hotspot analysis. The characterization results for 4 main categories show: Global Warming Potential 70.02 kg CO₂ eq, Ozone Layer Depletion 1.11E-06 kg CFC-11 eq, Acidification Potential 0.65 mol H+ eq, Marine Eutrophication 0.30 kg N eq, and Freshwater Eutrophication 2.17E-03kg P eq. The results also show that throughout the life cycle of this product, the largest contributor to environmental impacts is in the downstream phase, especially the user gas metering unit process. This is due to the 200 km of pipelines for product transportation from the Central Processing Platform (CPP) to the user gate. Pipeline parameters (Ecoinvent database) refer to long-distance pipelines with high capacity. In addition, hotspots were also identified in the core phase: gas measurement and chromatography, gas turbine generators, and flare gas.

Petrophysical Properties Estimation by Using Well Log and Core Data Interpretation for Tertiary Reservoir in Ajeel Oil Field

Understanding the petrophysical properties of reservoirs is paramount for assessing their characteristics and estimating the potential of oil-bearing formations. This study focuses on the tertiary reservoir in the Ajeel oil field, renowned for its heterogeneous carbonate nature and diverse production formations, including Jeribe, Dhiban, and Euphrates. The formation of the tertiary reservoir is evaluated through a comprehensive analysis of petrophysical properties utilizing well log data from well AJ-25 and core analysis data (routine and special analysis). The study reveals significant insights into the petrophysical properties of the formations. The effective porosity values for the Jeribe, Dhiban, and Euphrates formations are determined as 15.41%, 4.65%, and 9.85%, respectively, with lithology predominantly consisting of dolomite rock interspersed with limestone slices and anhydrite nodules. A high Secondary Porosity Index (SPI) indicates fractures. Archie's Parameters, obtained from a Pickett Plot, yield cement coefficient (m=1.8), saturation exponent (n=1.9), and tortuosity factor (a=1.19). Water saturation levels for the Jeribe, Dhiban, and Euphrates formations are 33%, 86%, and 81%, respectively, with porosity and water saturation cutoff values determined as 10% and 60%, respectively. Net to Gross of Jeribe, Dhiban, and Euphrates formation are 0.706, 0.029, and 0.011, respectively. Jeribe Formation is identified as an oil-bearing zone. In contrast, the Dhiban and Euphrates formations are identified as water-bearing zones. To enhance the accuracy of petrophysical assessments, modern well logging techniques, such as the Formation Micro Scanner log (FMI log), are recommended to investigate fractures and their impact on field performance, as traditional logs may not adequately capture these features. Additionally, our comparative analysis highlights superior petrophysical properties of the Euphrates Formation compared to the Jeribe Formation. Therefore, prioritizing drilling and completion activities in the Euphrates Reservoir within the field, contingent upon its positioning relative to the oil-water contact level, is suggested for optimizing reservoir performance.

Enhanced Rubber Yield Prediction in High-Density Plantation Areas Using a GIS and Machine Learning-Based Forest Classification and Regression Model

Rubber is a perennial plant grown for natural rubber production, which is used in various global products. Ensuring the sustainability of rubber cultivation is crucial for smallholder farmers and economic development. Accurately predicting rubber yields is necessary to maintain price stability. Remote sensing technology is a valuable tool for collecting spatial data on a large scale. However, for smaller plots of land owned by smallholder farmers, it is necessary to process productivity estimates from high-resolution satellite data that are accurate and reliable. This study examines the impact of spatial factors on rubber yield and evaluates the technical suitability of using grouping analysis with the forest classification and regression (FCR) method. We developed a high-density variable using spatial data from rubber plots in close proximity to each other. Our approach incorporates eight environmental variables (proximity to streamlines, proximity to main river, soil drainage, slope, aspect, NDWI, NDVI, and precipitation) using an FCR model and GIS. We obtained a dataset of 1951 rubber yield locations, which we split into a training set (60%) for model development and a validation set (40%) for assessment using area under the curve (AUC) analysis. The results of the alternative FCR models indicate that Model 1 performs the best. It achieved the lowest root mean square error (RMSE) value of 19.15 kg/ha, the highest R-squared (R2) value (FCR) of 0.787, and also the highest R2 (OLS) value of 0.642. The AUC scores for Model 1, Model 2, and Model 3 were 0.792, 0.764, and 0.732, respectively. Overall, Model 4 exhibited the highest performance according to the AUC scores, while Model 3 performed the poorest with the lowest AUC score. Based on these findings, it can be concluded that Model 1 is the most effective in predicting FCR compared to the other alternative models.

The Inhibitory Impact of a Co-Assembly Gel with Natural Carrier-Free Binary Small Molecules, as Used in Traditional Chinese Medicine, on the Viability of SW1990 Cells

Chinese herbs are a huge treasure trove of natural products and an important source of many active molecules. The theory of traditional Chinese medicine compatibility (TCMC) is widely applied in clinical practice, but its mechanism is still ambiguous. This study aims to open a new window for this predicament by studying the interaction between the main active ingredients from a drug pair. Carrier-free assembly of natural products improves the shortcomings of traditional nanodelivery systems and opens a new path for the development of new nanomaterials. The drug pair “Pueraria and Hedyotis diffusa” has been commonly used in clinical practice, with a predominant therapeutic effect. This study is devoted to the study of the binary small molecule co-assembly of the main active molecules from the drug pair. In this study, we introduce a carrier-free composite gel, formed by the co-assembly of puerarin (PUE) and deacetylasperulosidic acid (DAA) via non-covalent bonds including π–π packing, intermolecular hydrogen bonding, and C=O π interactions. With a strain point 7-fold higher than that of P gel, the P − D gel exhibited favorable rheological properties. The survival rate of SW1990 cells in the P − D group was only 21.39% when the concentration of administration reached 200 μM. It thus demonstrated activity in inhibiting SW1990 cells’ survival, suggesting potential in combating pancreatic cancer. Furthermore, this research offers a valuable concept for enhancing the mechanical properties and bioactivity of hydrogel materials through the utilization of a multi-component natural small molecule co-assembly approach. More importantly, this provides new ideas and methods for the treatment of pancreatic cancer and the analysis of traditional Chinese medicine compatibility theory.

Protective Effects of Spermacoce hispida Against Cisplatin-Induced Nephrotoxicity: A Study on Oxidative and Nitrosative Stress

Background: Nephrotoxicity is a common and severe side effect of cisplatin, a widely used chemotherapeutic agent. The mechanism of cisplatin-induced nephrotoxicity involves oxidative stress, inflammation, and apoptosis, leading to renal damage. There is growing interest in exploring natural products with antioxidant and anti-inflammatory properties as potential protective agents against drug-induced nephrotoxicity.Objective: The present study aimed to investigate the protective effects of Spermacoce hispida against cisplatin-induced nephrotoxicity in an in vivo rat model. Methods: S. hispida was collected, and plant extracts were prepared using different solvents. The prepared extracts underwent phytochemical screening. Nephrotoxicity was induced in rats through a single intraperitoneal injection of cisplatin at a dose of 5 mg/kg. S. hispida extracts at a dose of 100 mg/kg were administered to assess their protective activity. Key parameters measured included blood urea nitrogen (BUN), serum creatinine, oxidative stress markers, proinflammatory cytokines, nitric oxide (NO) levels, and histological alterations in kidney tissue.Results: Cisplatin treatment resulted in increased levels of BUN, serum creatinine, and proinflammatory cytokines in rats, indicating nephrotoxicity. However, treatment with S. hispida extracts for 14 days significantly decreased these elevated levels. Additionally, S. hispida treatment reduced oxidative stress and NO production in cisplatin-treated rats. Histological examination revealed that cisplatin induced structural damage in kidney tissues, which was normalized by S. hispida treatment. Conclusion: The study concludes that Spermacoce hispida exhibits nephroprotective activity, likely by inhibiting oxidative stress and NO production, thereby mitigating cisplatin-induced nephrotoxicity in rats

Cationic Curcumin Nanocrystals Liposomes for Improved Oral Bioavailability: Formulation Development, Optimization, In Vitro and In Vivo Evaluation

Curcumin, a naturally occurring poorly water-soluble polyphenol with a broad spectrum, is a typical BCS IV drug. The objective of this study was to develop curcumin nanocrystals liposomes with the aim of improving bioavailability. In this study, we prepared cationic curcumin nanocrystals with a particle size of only 29.42 nm; such a phenomenal range of particle sizes is very rare. Moreover, we summarized and evaluated the parameters of the nanocrystal preparation process, including methods, formulations, etc., and the rules we concluded can be generalized to other nanocrystal preparation processes. To counteract the instability of the nanocrystals in the digestive tract, cationic curcumin nanocrystals were loaded into negatively charged liposomes through gravitational force between different charges. Unexpectedly, chitosan oligosaccharide was found to promote the self-assembly process of curcumin nanocrystal liposomes. In vitro and in vivo experiments demonstrated that chitosan-modified curcumin nanocrystal liposomes exhibited enhanced resistance to enzyme barriers, mucus barriers, and cellular barriers, resulting in a 5.4-fold increase in bioavailability compared to crude powder formulations. It can be concluded that cationic nanocrystals liposomes represent an appropriate novel strategy for improving the dissolution rate and bioavailability of poorly soluble natural products such as curcumin.