Journal of Pharmaceutical and Biopharmaceutical Research

Blockchain technology for advanced therapy medicinal products: Applications in tracking, data sharing, and supply chain automation

Cristobal Aguilar-Gallardo — 2024-06-18

Advanced therapy medicinal products (ATMPs) like cell and gene therapies offer transformative treatment options for many diseases. However, coordinating the decentralized, patient-specific manufacturing of autologous ATMPs across multiple hospitals poses major supply chain challenges. This paper provides a comprehensive analysis of how blockchain technology can enhance decentralized ATMP manufacturing networks. First, background on ATMPs and complexities of decentralized production is reviewed. An overview of blockchain architecture, key attributes, and existing use cases then follows. The major opportunities for blockchain integration in ATMP manufacturing are discussed in depth, including tracking autologous products across locations, enabling data sharing between hospitals to power AI-based optimization, automating supply chain processes, and maintaining provenance records. Critical limitations around scalability, privacy, regulation, and adoption barriers are examined. Design considerations for developing blockchain ecosystems tailored to the unique ATMP environment are also explored. Blockchain shows immense promise for transforming visibility, coordination, automation, and data unification in decentralized ATMP manufacturing networks. Despite current challenges, blockchain is prepared to profoundly impact the advancement of personalized cell and gene therapies through enhanced supply chain instrumentation. This paper provides a comprehensive analysis of this emerging technological innovation and its applications to address critical needs in ATMP translation and manufacturing.

Anticonvulsant activities of the methanol crude extract and fractions of the leaf Solanum americanum (S.a.) in pentylenetetrazole and 4-amino pyridine induced seizure in white albino rats

Rita Nwabiani — 2024-05-31

This research investigated the anticonvulsant effect of the crude extract and fractions of Solanum americanum’s (S.a.) leaves on seizures induced by pentylenetetrazole (PTZ) and 4- amino pyridinein albino rats to authenticate the use of the leaves in the treatment of epilepsy in South -Eastern Nigeria. The leaves of S.a were extracted with methanol and fractionated using n-hexane, ethyl acetate and methanol. The parameters observed were onset of convulsions in minutes, duration of clonic phase in minutes, percentage protection from seizures and mortality. The anticonvulsant tests were carried out using 60 (sixty) white albino rats (weighing 80-136 g) of both sexes, varying concentrations of both methanol extracts and fractions (12.5, 25.0, 50.0, 100 and 200 mg/kg b.w.) were administered to the rats after which convulsion were induced in the rats using 9.0 mg/kg of PTZ and 1.5 mg/kg 4-amino pyridine on different groups (35 and 25) of rats respectively. The results of the various groups were compared with the control group and significance was analyzed by one-way ANOVA. The acute toxicity test was conducted at a dose of 3000 mg/kg. At a peak dose of 200 mg/kg methanol crude extract, hexane and methanol fraction in PTZ model protected the animals from seizure at 89.30%, 100%, 100% but gave 80%, 80% and 60% protection from mortality respectively. Hexane fraction (12.5, 25, 50, 100 and 200 mg/kg) protected the rats against mortality at 20%, 40%, 60%, 60% and 80% respectively, while no anticonvulsant activities were detected in ethyl acetate fraction. Differences among the means and standard deviation was statistically significant at P < 0.05.The acute toxicity test showed that the leaf of S.a. is non-toxic. The result obtained substantiated the use of the leaf of Solanum americanum ethnobotanically as anticonvulsant.

A big threat : Aflatoxin

Ritu Tiwari — 2024-05-22

The past decade has witnessed a tremendous surge of interest in herbal medicines throughout the world. Aflatoxins are naturally occurring mycotoxins that are mainly produced by Aspargillus flavus and Aspargillus parasiticus and primarily contaminate food crops such as corn, groundnuts, and tree nuts as well as herbal medicinal plants in tropical and subtropical regions of the world. It is a lethal substance that intensely or at slower ingestion influences the strength of humans and animals. Aflatoxin study is vital for a safety perspective as they are extremely lethal and cancer-causing; to overcome the health effect of aflatoxins and for better assessment and standardization of herbal plant drugs. The investigation includes worldwide regulations on aflatoxins with their acceptable ranges in commodities. With more controls for adequate dimensions of aflatoxins set up, present-day analytical techniques have turned out to be very modern, capable of accomplishing results with high accuracy and precision, appropriate for administrative research centers and post-reap sample testing in developed countries.

Determination of pesticide residues and heavy metals in Adhatoda Vasaka Linn.

Ritu Tiwari — 2024-05-15

Heavy metals and pesticide residue analysis plays an important role in the quality control of medicinal plants like Vasaka (Adhatoda vasica). Hence a study was conducted to determine heavy metals and pesticide residues in this medicinal herb, which is a highly useful commodity in the health system. The reliable, rapid and nontoxic sample preparation method like QuEChERS and analytical methods like GC-MS were proposed for the simultaneous determination of pesticide residues and Heavy metal detection was carried out by ICP-MS. In this study, the presence of organophosphorus and organochlorine pesticides like alachlor, heptachlor, heptachlor epoxide, aldrin, dieldrin, endrin, etc was checked but not detected. Heavy metals like Arsenic (As), Cadmium (Cd), Mercury (Hg) and Lead (Pb) are traced in samples about 2.3005 ppb, 0.799 ppb, 2.290 ppb and 10.204 ppb respectively in the present study.

TAAR1 as a new target for the treatment of bipolar disorder: Anti-manic and anti-depressant activity of the novel agonist PCC0105004

Linyao Yu — 2024-03-25

Background: Bipolar disorder (BD) is a deleterious psychiatric disorder, and the available pharmacotherapies have limited efficacy with significant side effects. Trace amine-associated receptor 1 (TAAR1) is an emerging drug target for neuropsychiatric disorders such as schizophrenia and substance user disorders. However, it is unknown whether TAAR1 is involved in the pathogenesis of BD. This study examined the effects and underlying mechanisms of a novel TAAR1 agonist, PCC0105004, in a rat model of ouabain (OUA)-induced BD.
Methods: Intracerebroventricular (ICV) administration of OUA-induced BD model was established. The in vitro cell-based cAMP assay was used to examine TAAR1 agonism of PCC0105004. The receptor specificity of PCC0105004 was determined by an off-target panel assay that included radioligand binding and enzymatic assays. The effects of PCC0105004 on manic-like and depressive-like behaviors were evaluated in the rat BD model. TAAR1-mediated signaling and oxidative stress parameters were biochemically determined in the prefrontal cortex and the hippocampus of rats.
Results: Western blotting revealed reduced TAAR1 expression level in the prefrontal cortex but unchanged in the hippocampus in model rats. PCC0105004, a TAAR1 agonist with the agonism EC₅₀ value of 0.06182 μM, attenuated the manic-like behaviors on the 7th day and the depressive-like behaviors on the 14th day at doses that did not affect locomotor activity in the BD rats. Mechanistically, PCC0105004 exerted its behavioral effects via the reduction of ROS damage through the phosphorylation activation of the TAAR1/Akt/GSK3β/BDNF signaling pathway.
Conclusion: These results demonstrated the potential antimanic-like and antidepressant-like efficacy of a novel TAAR1 agonist PCC0105004 in rats and revealed its underlying molecular basis, which supports the possibility of TAAR1 agonists as candidate pharmacotherapeutics for BD.

A novel role of NK3 receptor signaling in bipolar disorder

Wei Zhang — 2024-03-14

Objective: Bipolar disorder (BD) affects more than 1% of the global population with limited therapeutic options. The neurokinin B (NKB)-neurokinin B receptor (NK3R) is involved in a variety of emotional activities. This study explored the role of NK3 receptor signaling in bipolar disorder.
Materials and methods: In this study, a model of intracerebroventricular (ICV) administration of OUA-induced BD was used to investigate the possible role of NK3R signaling in BD. The involvement of NK3R in the expression of OUA-induced BD was assessed by genetically knocking down the NK3R-encoding TACR3 gene with shRNA approach in the hippocampus and systemic administration of a NK3R antagonist ESN364,. Biochemical techniques were used to examine the NK3R-associated signaling changes and the oxidative stress parameters in the hippocampus of BD rats.
Results: The NK3R expression level was elevated in the hippocampus BD rats. Both TACR3 knockdown in the hippocampus and ESN364 treatment reversed the manic-like and depression-like behaviors in BD rats Inhibition of the NK3R signaling reversed oxidative stress-induced damage via upregulating the BDNF signaling pathway in the hippocampus.
Conclusion: These results demonstrated that NK3R signaling plays a key role in the pathogenesis of BD and that pharmacological antagonist of NK3R such as ESN364 could represent a novel therapeutic strategy for the management of BD.

Network pharmacology-based prediction for therapeutic mechanism of FuYueKang Lotion on acute eczema

Xiaowen Wen — 2023-11-01

Objective: Fuyuekang Lotion (FYKL) is an improved traditional Chinese medicine (TCM) prescription widely used to treat acute eczema (AE). However, the mechanism of action remains unclear. This study aimed to explore the therapeutic mechanism of FYKL in AE.
Methods: We revealed the underlying mechanism by utilizing a network pharmacology approach, molecular docking studies, and in vitro verification. The active compounds in FYKL were identified, and their targets were predicted. These targets were subsequently mapped to a component-target interaction network, with their therapeutic mechanisms predicted through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to verify protein-binding efficacy. Potential key targets of FYKL against AE were further confirmed via reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Results: The study identified 59 potential active compounds of FYKL, with quercetin, luteolin, and gallic acid suggested as critical active ingredients. Our findings suggest that these ingredients could exert their effects mainly by modulating the inflammatory immune response and promoting epidermal repair. FYKL was found to be a multi-target, multi-component drug that could potentially regulate the inflammatory immune response in AE through numerous pathways.
Conclusions: The findings from this study provide a scientific basis for further research into the therapeutic effects and mechanisms of FYKL in treating AE, underscoring the potential of TCM in modern therapeutics.

Exploring the mechanism of three herb pairs for the treatment of atherosclerosis through network pharmacology and molecular modeling

Minjun Wang — 2023-04-19

Background: Atherosclerosis (AS) is one of the leading causes of cardiovascular diseases. The traditional China herb pairs such as Huanglian-Gualou, Honghua-Taoren, and Suhexiang-Bingpian showed therapeutic effects on AS by clearing heat and resolving phlegm, invigorating blood and removing blood stasis, as well as aromatic resuscitation, respectively. However, the common and specific mechanisms of these pairs against the same disease are elusive.
Objective: This study aimed to explore the molecular mechanisms of 3 herb pairs treating AS by network pharmacology, molecular modeling and mechanism experiments.
Methods: The components and their corresponding targets of 3 herb pairs, as well as AS-related targets, were collected from multiple databases and literature. Then the protein-protein interaction network was built to identify the key components and targets associated with AS. The pathway enrichment analysis using KEGG was carried out for analyzing the common mechanisms of 3 herb pairs against AS. Finally, the binding modes of the key components and targets were analyzed by molecular docking and molecular dynamic simulation.
Results: The PPI network indicated that the common targets of 3 herb pairs focused on four pathways, including regulated vascular shear stress, TNF, ARE-RAGE, and IL-17 pathways. The molecular docking analysis indicated that the key component quercetin showed highest docking score with PTGS2 in comparison to other targets. Molecular dynamics simulations revealed that quercetin stably anchored to the active pocket of PTGS2 by forming hydrogen bonds with Thr175, Asn351, and Trp356.
Conclusion: The molecular mechanism of Huanglian-Gualou, Honghua-Taoren, and Suhexiang-Bingpian against AS was preliminarily expounded, and we wish to provide a theoretical instruction for clinical treatment of AS.

LPM570065 ameliorates anxiety-like and depressive-like behaviors in CUMS rats through regulating DNA methylation in hippocampus

Shengmin Ji — 2023-04-17

Objective: This study aims to analyze the effects and underlying mechanisms of LPM570065 on behavioral phenotypes in rats with generalized anxiety disorder (GAD).
Methods: The chronic unpredictable mild stress (CUMS) rats were used to observe the results of LPM570065. Total 72 male Sprague Dawley rats were divided into control, vehicle (0.5% CMC-Na), LPM570065 (32 mg/kg) and diazepam (3 mg/kg) groups, 12 rats in each group. Anxiety-like behaviors of rats were observed by elevated zero maze test and novelty-suppressed feeding test. Depressive-like behaviors of rats were detected by forced swimming test. DNA methylation in hippocampi of rats were measured by reduced representation bisulfite sequencing (RRBS). In hippocampi of rats, expressions of DNA methyltransferase (DNMT) 1 and DNMT3a proteins were measured by western blot, and density of dendritic spines was observed by Golgi staining.
Results: Compared with the control group, the weights of rats were obviously decreased (p < 0.001) and the rats showed anxiety-like and depressive-like behaviors (p < 0.001) in the vehicle group. Compared with the vehicle group, the weights of rats were significantly increased (p < 0.001) and the anxiety-like and depressive-like behaviors were improved (p < 0.001) in the LPM570065 group. The results of RRBS showed that there were 49964 promoters showed hypermethylation in the LPM570065 treatment rats contrasted to the vehicle treatment rats. In addition, these promoters were enriched in signal transduction and immune function. Furthermore, the expressions of DNMT1 and DNMT3a were significantly decreased, the density of dendritic spines was significantly increased in hippocampi of LPM570065 treatment rats compared with the vehicle treatment rats.
Conclusions: LPM570065 ameliorates anxiety-like and depressive-like behaviors in CUMS rats, and its mechanism is possible associated with downregulating DNA methylation in hippocampus.

(E)-2-Benzylidenecyclanones: Part XVII. An LC-MS study of microsomal transformation reactions of (E)-2-[(4'-methoxyphenyl)methylene]-benzosuberon-1-one: A cyclic chalcone analog

Fatemeh Kenari — 2023-03-22

Biotransformation of the antiproliferative (E)-2-[(4’-methoxyphenyl)methylene]-benzosuberon-1-one (2c) was studied using rat liver microsomes. As a result of the CYP-catalyzed transformations, one monooxygenated (2c+O) and the demethylated (2c-CH₂) metabolites were identified by HPLC-MS. (E)-2-[(4’-methoxyphenyl)methylene]-benzosuberon-1-ol, the expected product of rat liver microsomal carbonyl reductase, was not found in the incubates. Microsomal GST-catalyzed reaction of the compound resulted in formation of diastereomeric GST-conjugates. Under the present HPLC conditions, the diastereomeric adducts were separated into two chromatographic peaks (2c-GSH-1 and 2c-GSH-2).