Current Pharmaceutical Biotechnology - Online First

Diabetes is a chronic metabolic disease that affects individuals of all ages. Therefore, there is an urgent need to develop novel therapeutic agents from natural sources. In this context, Hibiscus cannabinus was selected for the present investigation. The study aimed to evaluate the hypoglycemic, hypolipidemic, and antioxidant activities of Hibiscus cannabinus extract in a streptozotocin-induced diabetic model in Wistar rats.

An in vivo study was planned to evaluate the hypoglycaemic, hypolipidemic, and antioxidant effects activities of HCE. Thirty-six male Wistar rats were randomly divided into six groups, and diabetes was induced by a single acute intraperitoneal injection of STZ. Animals were treated orally with HCE at doses of 100, 200, and 400 mg/kg b.wt., or with Glibenclamide (5 mg/kg b.wt.), along with a normal control group. The rats were monitored for body weight, feed intake, blood glucose and insulin levels, lipid profile, and markers of lipid peroxidation and antioxidant activity.

HCE showed a significant reduction in blood glucose levels, improved lipid profile, enhanced antioxidant enzyme activity, and decreased lipid peroxidation in diabetic rats in a dose-dependent manner compared with the control group. Notably, the 400 mg/kg b.wt. HCE group exhibited efficacy comparable to that of the Glibenclamide treatment group.

HCE showed activity in streptozotocin-induced diabetic rats, indicating its potential as a natural therapeutic agent. Further investigation into its mechanisms and clinical applicability for managing diabetes-related complications is needed to support its pharmaceutical use.

HCE extract exhibited strong antidiabetic, lipid-lowering, and antioxidant activities in STZ-induced diabetic rats.

Ropivacaine (RPV), a commonly used local anesthetic, is limited in its effectiveness for postoperative pain management due to its short duration of action. To address this issue, this study further explores the development of poly(lactic-co-glycolic) acid (PLGA)-PVA nanocarriers designed to extend RPV's release and efficacy.

PLGA-PVA-RPV nanocarriers were synthesized via an emulsion technique and comprehensively characterized using transmission scanning electron microscopy, Malvern ZS90, and Fourier transform infrared spectroscopy. The cytotoxicity of these nanocarriers against HaCaT cells was determined using the Cell Counting Kit-8 viability assay and calcein-acetoxymethyl/ propidium iodide staining. Flow cytometry and scratch assays were used to assess their effects on the HaCaT cell cycle, apoptosis, and migration.

The PLGA-PVA-RPV nanocarriers exhibited a spherical morphology, small size (10.90 ± 2.19 nm), uniform distribution, and stable zeta potential (−7.93 ± 0.81 mV). The PLGA-PVA-RPV nanoparticles demonstrate excellent biocompatibility; even at a high concentration of 1000 μg/mL, the cell viability remains above 80%, which is significantly higher than that of the free RPV group (67.3%, P < 0.05). Further mechanistic studies showed that PLGA-PVA-RPV nanoparticles induced cell cycle arrest and inhibited cell migration, collectively demonstrating their low toxicity, excellent biocompatibility, and sustained-release potential.

The PLGA-PVA-RPV nanocarriers demonstrate enhanced efficacy and biocompatibility for prolonged ropivacaine release, offering a promising strategy for postoperative pain management. Future work should focus on in vivo validation and parameter optimization to facilitate clinical translation.

PLGA-PVA-RPV nanocarriers possess optimal physicochemical properties (small size, homogeneity, stability) and superior biosafety, providing a promising strategy for extending RPV's analgesic efficacy. This technology has significant potential to improve postoperative pain management.

Dihydromyricetin (DMY), a phytoflavonoid with diverse pharmacological activities, is limited in cosmetic applications by poor solubility, easy discoloration, and low bioavailability. This study aimed to address these drawbacks for its practical cosmetic use.

DMY nanoliposomes (DMY-NL) were prepared via ethanol injection-high-pressure homogenization, with orthogonal tests optimizing the process using particle size, PDI, and zeta potential as indices. Tests included in vitro dialysis-based sustained-release assay, erythrocyte hemolysis/human patch tests (safety), and DPPH scavenging/hemolysis/human patch anti-irritation tests (soothing efficacy).

DMY-NL had >90% encapsulation efficiency, 90-day stability under different storage conditions, and 48-h sustained release (superior to control). Safety was confirmed by hemolysis and patch tests; soothing efficacy was verified via DPPH scavenging and anti-irritation tests.

DMY-NL’s high encapsulation, good stability, and sustained release solve DMY’s cosmetic application limitations. Confirmed safety and soothing effects support its practical use in cosmetics.

This study provides a theoretical and practical basis for DMY’s cosmetic application, expected to expand its use in the cosmetic industry.

Neurodegenerative diseases are a group of life-threatening conditions characterized by gradual and severe neuronal degeneration, posing a significant global health challenge. Many neurodegenerative diseases, including Alzheimer's disease and Parkinson’s disease, share identical and recognizable etiologies, such as neuronal degeneration, apoptosis, oxidative stress, lipid peroxidation, Ca²⁺ overload, neuroinflammation, protein aggregation, endoplasmic reticulum stress, and mitochondrial dysfunction. Among these etiologies, oxidative stress and mitochondrial dysfunction are the primary contributing factors, involving several enzymes and signaling molecules in the underlying mechanism of disease progression. Globally available treatments provide only temporary symptomatic relief with side effects, and yet there is no medication to eradicate the disease-related cause.

Extensive research has explored novel herbal medications offered as neuroprotective against these debilitating conditions, aiming to reverse or halt the disease progression with minimal adverse effects. Pinostrobin is a major bioactive flavonoid primarily isolated from Boesenbergia rotunda (Fingerroot). Established research has reported that pinostrobin exhibits a wide array of pharmacological activities, including anti-inflammatory, anti-leukemia, antioxidant, antimicrobial properties, as well as protective effects against mitochondrial dysfunction and neurodegeneration.

Based on preclinical studies, we have summarised the current knowledge of pinostrobin's neuroprotective actions, highlighting its effectiveness in mitigating neuronal damage, preserving synaptic function, reducing oxidative stress, neuroinflammation, protein aggregation, mitochondrial apoptosis, and calcium overload. These mechanisms collectively support its therapeutic potential in modulating the molecular pathways underlying Alzheimer’s and Parkinson’s disease.

This review offers a comprehensive analysis of pinostrobin and its molecular pathways in combating neurodegenerative diseases, highlighting its promising effectiveness as a natural neuroprotective agent in Alzheimer’s and Parkinson’s disease by modulating mitochondrial and oxidative stress-mediated pathways.

Ganoderma lucidum is considered a medicinal mushroom, as it primarily improves gut health by modulating the gut microbiota. As an abundant source of bioactive metabolites, antioxidants, and industrial enzymes, mushrooms make significant contributions to functional foods, nutrition, and pharmaceuticals. Polysaccharides derived from G. lucidum exhibit prebiotic potential, promoting the growth and activity of beneficial gut microorganisms.

This systematic review examines the impact of white rot basidiomycetes metabolites on colorectal cancer treatment. We have compiled and analyzed data from PubMed, Google Scholar, and ResearchGate, presenting a comprehensive report with a table for clear understanding.

Evidence from in vivo and in vitro studies demonstrates that G. lucidum has potential as a gastrointestinal cancer inhibitor by inducing pro-apoptosis, autophagy, G0/G1 cell cycle arrest, and immunomodulation.

Bioactive metabolites and polysaccharides have prebiotic potential, enhancing the growth and activity of beneficial gut microorganisms that may lower the risk of gastrointestinal cancers by modifying gut bacteria. The prebiotic properties may boost immunity, reduce inflammation, and strengthen intestinal barrier integrity.

The current review explores the therapeutic potential of G. lucidum and other medicinal mushrooms as dietary supplements, focusing on their impact on the gut microbiome and gastrointestinal cancer.

Generalized anxiety disorder (GAD) is a prevalent and intricate mental disorder that significantly impairs the quality of life of patients. Currently, the exact etiology of GAD remains incompletely understood. Consequently, the discovery of novel drug targets for GAD is highly important.

We obtained cis-eQTL data of druggable genes from the eQTLGen Consortium as the exposure data and GWAS data of GAD from the FinnGen Database as the outcome. The impact of druggable genes on GAD was simulated through Mendelian randomization analysis. Subsequently, a colocalization analysis was conducted to calculate the probability of shared pathogenic variants between the cis-eQTLs of druggable genes and GAD. To further validate our findings, a summary data-based Mendelian randomization (SMR) analysis was carried out.

Mendelian randomization (MR) analysis identified 24 druggable genes with potential causal relationships, among which genetically predicted increased KDM5A levels were associated with a higher risk of GAD (OR=1.0991, 95% CI: 1.0021–1.2056, P=0.0451), suggesting a potential role of KDM5A gene expression in the pathogenesis of GAD. The GAD and KDM5A genes might share a causal variant. The SMR further verified the accuracy of the KDM5A gene.

MR analysis identified KDM5A as a promising therapeutic target for GAD, with additional potential from genes, like MERTK and PPT1. However, the effectiveness of the relevant drug targets requires further validation.

This study suggested that the KDM5A gene might be a potential therapeutic target for treating GAD, providing a direction for future drug development in GAD patients.

The current pharmaceutical industry has increasingly adopted artificial intelligence (AI), integrating it across the entire industrial chain. While AI improves efficiency and reduces costs, it also faces challenges. This study explores both the technological evolution and contemporary innovation hotspots of AI in pharmacy.

This study adopts a fusion analysis of multi-source data, constructing a bi-dimensional analytical framework based on patented inventions (1990-2024) and research articles (2020-2024) as research objects. The study applies the Latent Dirichlet Allocation (LDA) topic model to analyze the evolution of patent topics and employs CiteSpace to construct keyword knowledge graphs from research articles. By integrating patent and article data to define technical labels, the study identifies research hotspots from the perspective of the pharmaceutical life cycle, enabling cross-validation from both scientific and technical dimensions.

The number of AI-related patents in the pharmaceutical field has grown rapidly over the past five years. Technological topics exhibit a distinct evolutionary trend. Research hotspots span the entire pharmaceutical life cycle, from drug development to clinical delivery. Additionally, potential directions for future technological development have been identified.

Research hotspots in the application of AI in pharmaceuticals include target identification, virtual screening, drug delivery, clinical trials, and pharmacovigilance. Precision medicine and explainable AI (XAI)-driven pharmacy modeling are expected to emerge as key directions for future technological development.

AI has already reshaped the pharmaceutical industry through applications across all stages of the pharmaceutical life cycle. It is poised to attract growing research attention and drive innovative applications in the years ahead.

FLRCC is a rare renal carcinoma subtype caused by FH mutations, categorized into hereditary (germline mutations) and sporadic (somatic mutations) forms. These forms are clinically and pathologically similar, complicating differentiation without genetic testing. The aim of this study is to investigate the clinicopathological and molecular genetic differences between hereditary and sporadic fumarate hydratase (FH)-deficient leiomyomatosis and renal cell carcinoma (FLRCC) to improve diagnostic accuracy and clinical management.

A retrospective analysis of 14 FLRCC patients was conducted(May 2020-August 2023). Immunohistochemistry (FH, 2SC, p16), HE staining, and next-generation sequencing (NGS) of tumor tissues and blood leukocytes were performed.

The 14 patients with FH-deficient leiomyoma were 25-54 years old, with a mean age of 36.21 ± 8.16. 78.5% (11/14) had clinical symptoms and multiple, large-sized fibroids (median maximum volume was 75 mm). Patients with leiomyoma and FH deficiency were divided into hereditary and sporadic FLRCC based on FH gene sequencing. Patients with HLRCC had an earlier onset, and the serum tumor marker CA125 was more significant. Moreover, tumor tissues from patients with hereditary and sporadic FH-deficient LRCC differed in immunohistochemical and HE staining characteristics, including more positive p16 and greater susceptibility to invasion and metastasis in patients with HLRCC, as well as malignant proliferation in patients with sporadic FH-deficient LRCC.

Although limited by sample size, our preliminary findings indicated subtle differences in the age of onset, as well as immunohistochemical and histopathological features of hereditary and sporadic FH-deficient LRCC, facilitating the understanding and clinical diagnosis of FLRCC.

In clinical diagnosis, all information should be fully integrated, and a comprehensive judgment should be made to make a correct pathological diagnosis and provide targeted treatment for patients with an FH gene mutation.

This study investigated the role and potential mechanisms of discoidin domain receptor 1 (DDR1) in colon fibrogenesis.

We employed the DSS-induced chronic colitis and fibrosis model to evaluate the therapeutic potential of DDR1 knockout on colonic fibrosis. In vitro experiments involved generating human normal colonic epithelial cells (HIEC line) with DDR1 overexpression by lentivirus transfection. Human colonic fibroblasts were exposed to conditioned medium (CM) from the stably transfected cells that had been treated with transforming growth factor-beta 1 (TGF-β1). The cells were collected for molecular and biochemical analyses.

Our proteomics analysis of DDR1 indicated significant enrichment of proteins involved in the extracellular matrix and fibrosis. In DSS-treated DDR1-KO mice, attenuation of colonic fibrosis and reduced activation of colonic fibroblasts were observed, contrasting significantly with their counterparts in DSS-treated WT mice. Colonic fibroblasts exhibited a marked increase in α-smooth muscle actin and type I collagen expression when exposed to CM from HIEC cells with DDR1 overexpression. Finally, overexpression of DDR1 markedly elevated the levels of p-PI3K, p-Akt, p-mTOR, p62, and LC3B in HIEC cells, resulting in enhanced secretion of TGF-β1.

DDR1 in HIEC cells attenuates autophagy primarily by activating the PI3K/AKT/ mTOR signaling axis and concurrently increasing the autophagic markers LC3B and p62, thereby inducing paracrine secretion of TGF-β1, which drives the activation and proliferation of colonic fibroblasts and elicits a robust profibrotic response.

Our study suggests that DDR1 may be a potential therapeutic target for colonic fibrosis.

Rabies Virus (RV or RABV) is a neurophilic pathogen predominantly transmitted to humans through bites, scratches, or wounds. Upon entering the central nervous system, the virus can cause severe symptoms, including acute encephalitis and paralysis, ultimately leading to death with an almost 100% mortality rate. Hence, it is essential to develop an effective oral rabies vaccine.

We designed and synthesized three modified 5'-cap mRNA vaccines (RV-01(CAP-01), RV-01(CAP-02) and RV-01(CAP-03)) encoding rabies virus glycoproteins in vitro and evaluated their immunogenicity and protective effect in mice.

The modified 5'-cap vaccine was successfully constructed and could be effectively expressed in HEK293 cells. The antibody detection results revealed the abundance of RABV-G in RV-01(CAP-01), RV-01(CAP-02) and RV-01(CAP-03). ELISPOT assays indicated that these variants promoted the production of immune-related cytokines. Furthermore, the modified 5'-cap vaccines could reduce the rabies viral load of mice and effectively prolong their survival.

The rabies mRNA vaccine had high efficacy and safety in preventing rabies, suggesting the great potential of mRNA as a promising candidate for RABV vaccines. However, the potential causes of the differences in the performance of the three modified 5'-cap rabies mRNA vaccines and the clinical application of 5’-Cap altered rabies mRNA vaccines need to be explored.

Hence, these results demonstrated that the modified 5’-cap mRNA vaccine was effective in inducing immune responses, which might be considered a promising prophylactic strategy for rabies.

Breast cancer is a global health challenge with a high mortality rate of 30% of total cases in a year. Breast cancer presents in 4 main types, namely, TNBC, HER2+, luminal A, and Luminal B. Current treatments, though not without side effects, incur substantial cost, and are rendered ineffective by rising drug resistance. Phytochemicals are being investigated for their beneficial effects on breast cancer. Systematically collecting, organizing, and analyzing this data from available literature could benefit the development of more potent chemopreventive and chemotherapeutic approaches with reduced side effects.

To overcome the challenges posed by diverse naming practices, we adopted a sentiment (subjective) based text-mining approach to systematically extract and analyze data on anti-breast cancer phytochemicals from biomedical literature. This method is based on anchor and associated terms to capture authors’ sentiments regarding the therapeutic potential of these compounds. Subsequently, comprehensive and objective information was extracted and curated for each phytochemical, including target genes, pathways, study type, IC50 values, PMIDs, plant sources, and geographical availability.

PhytoCAT (PhytoChemical Affordable Therapeutics for Breast Cancer) is a comprehensive database of phytochemicals, plant extracts, and essential oils, enriched with links to phytogeographic data and chemical structures. PhytoCAT includes data on 28 essential oils, 470 plant extracts, and 1,649 phytochemical compounds. These compounds were classified into several chemical groups, including alkaloids (167), coumarins (43), flavonoids (290), lignans (47), quinones (43), saponins (27), sesquiterpenoid lactones (40), terpenoids (282), triterpenoid saponins (28), and xanthones (22) groups. Additionally, 505 phytochemicals belong to other subclasses such as esters, glucosides, phenanthrenes, and phenylpropanoids. Further, information on their mechanisms of action is also provided.

Phytochemicals have gained significant attention in recent years because of their potential health benefits, particularly in the prevention and treatment of various diseases, including cancer. Compounds such as curcumin, resveratrol, and epigallocatechin gallate (EGCG) are examples of phytochemicals that have shown promise in preclinical studies. PhytoCAT offers a centralized and searchable database enriched with biological, chemical, and pharmacological details. Its structured presentation allows researchers to identify promising compounds and study patterns in chemical class-specific activity.

PhytoCAT provides an evidence-based platform for researchers and clinicians to explore the potential of phytochemicals in breast cancer management. Although PhytoCAT has an advanced search engine, it lacks analytical tools, which we envisage integrating in the future. future. (https://phytocat.igib.res.in/)

Radiation targets cancer but risks causing infertility by damaging sensitive testes, especially spermatogonia. This study investigates IR-induced testicular damage and assesses PGZ's potential protective role as a ferroptosis inhibitor.

In this study, Seventy-two BALB/c mice were randomly divided into eight groups: a control, PGZ (10, 20, and 30 mg/kg), IR (8 Gy), and IR+ PGZ (in three doses). PGZ was administered for 10 consecutive days, and mice were exposed to IR on the 11^th day of the study. 24 h after RT, the mice's testis tissue was subjected to a series of evaluations to assess oxidative stress and antioxidant parameters, with histopathological analyses conducted one week after IR.

Biochemical analyses revealed that exposure to IR significantly increased ferroptosis markers, while concurrently decreasing intracellular antioxidants GSH. Histological examinations confirmed damage to spermatogenic cells, leading to detachment from the basement membrane and reduced sperm counts. Pre-treatment with PGZ at 30 mg/kg effectively reduced the levels of oxidative stress markers and improved antioxidant levels, demonstrating its potential protective effects against ferroptosis.

The results suggest PGZ can protect against radiation-induced testicular damage by inhibiting ferroptosis and promoting spermatogenesis recovery.

These results indicate that PGZ may act as a protective agent against radiation-induced testicular damage and support the recovery of spermatogenesis following IR exposure. Further research is warranted to explore the molecular mechanisms of PGZ's protective effects.

The research on traditional Chinese medicine (TCM) has experienced the transition from qualitative research to quantitative study. The application of mathematical modeling for data processing and analysis offers a more efficient and precise approach compared to conventional methods, enabling the timely acquisition of key efficacy indicators for preliminary evaluation. Therefore, the concept of mathematical modeling has been proposed to form a systematic theoretical system of TCM and diseases.

The article reviews the application of mathematical models in the research of traditional Chinese medicine in terms of compounding, extraction, optimization, quality evaluation, production, new drug development, pharmacokinetics, pharmacodynamics, and clinical symptom analysis. Relevant Chinese and English literature was obtained from PubMed, Cochrane Library, China Science and Technology Journal Database (VIP), Wanfang Data, CNKI and China Biomedical Literature Database (CBM).

We have found that integrating the concept of mathematical modeling with TCM theory has shortened the cycle of extracting active ingredients in traditional Chinese medicine and the development of new drugs, while also accelerating the realization of maximum clinical efficacy.

However, the comprehensiveness and precision of existing databases remain areas for improvement. In the future, further integration of multi-disciplinary technologies will be essential to advance the convergence of traditional medicine and modern science.

This review explores the application of mathematical models in the study of traditional Chinese medicine. It is evident that mathematical modeling has played a pivotal role in promoting fundamental research and the modernization of TCM.

This study aims to examine the impact of Rukangyin (RKY) and its components, LSQR and QTSS, on various cellular processes and signaling mechanisms in MDA-MB-231 triple-negative breast cancer (TNBC) cells.

Twenty-five Sprague-Dawley (SD) rats were randomly assigned to five groups according to the administered drugs, including the RKY group, LSQR group, QTSS group, fluorouracil group, and blank control group (n=5 in each group). The serum samples from each group were then used as a medicated medium for the culture of the TNBC cell line MDA-MB-231. Cell viability tests, apoptosis detection tests, and migration and invasion tests were used to evaluate the cytotoxicity of treated serum. YAP, TAZ, MST1, and LATS1 protein expression and phosphorylation were examined using conventional western blotting methods.

RKY and its QTSS and LSQR components significantly inhibited cell growth and promoted apoptosis in MDA-MB-231 cells. RKY also significantly blocked cell motility with a comparable effect to that of fluorouracil. All serum groups suppressed YAP and TAZ expressions while increasing p-YAP, p-TAZ, MST1, and LATS1 levels, with RKY showing superior efficacy.

In TNBC cells, RKY appears to enhance the tumor-suppressing signals of the Hippo signaling pathway via MST1, LATS1 activation, while restricting its pro-oncogenic action via YAP and TAZ blockade. However, in vivo and animal model experiments are required to confirm these findings.

RKY-medicated serum effectively inhibits growth, induces apoptosis, and reduces motility in the MDA-MB-231 cell line of breast cancer. This therapeutic potential of RKY on TNBC cells draws attention to the need for more investigations.

Cardiovascular diseases (CVDs) are the leading cause of death globally, often complicated by thromboembolic events. Plasmin, a key enzyme in fibrinolysis, is crucial for managing these conditions. Elevated or reduced plasmin levels can indicate thrombotic risks, making it a valuable diagnostic marker. Recent biotechnological advances have developed diagnostic kits to measure plasmin activity, aiding early detection and intervention. Fungal proteases, particularly from micromycetes, are emerging as promising agents in anticoagulant therapy. This study investigates three Aspergillus species — A. caespitosus, A. jensenii and A. neotritici for their potential to produce novel biomedical components.

The fungi were cultured, and their proteolytic profiles were analyzed. Key findings include the identification of specific proteases with plasmin-like and protein C-activating activities. These enzymes were purified using isoelectric focusing and characterized through SDS-PAGE and zymography.

The study confirmed that A. jensenii, and A. neotritici produce proteases with plasmin-like activity, with A. neotritici showing a single 35 kDa non-specific protease, and A. jensenii exhibiting two proteases (33 kDa and 100 kDa) in the acidic zone and one (110 kDa) in the neutral zone, the latter exhibiting specific chymotrypsin and plasmin-like activity.

Among the studied strains, A. neotritici exhibited the fastest secretion of proteases with plasmin-like activity, making it a promising source of enzymes with potential clinical applications. In contrast, A. caespitosus and A. jensenii displayed more complex protease compositions, featuring multiple active enzymes. Notably, one of the A. jensenii proteases showed pronounced specificity toward chymotrypsin and fibrinolytic substrates, indicating its suitability for the development of targeted therapeutic agents.

These findings suggest the potential of these fungal proteases for developing novel anticoagulant therapies and diagnostic tools.