integrated-uhplc-msms-hrms-strategy-for-screening-potentially

Integrated UHPLC-MS/MS and HRMS Strategy for Screening Potentially Hepatotoxic Furan-Containing Compounds in <em>Dioscorea bulbifera</em> L.

Dioscorea bulbifera L. (DBL), a traditional herbal medicine used to treat thyroid disorders and tumors, has raised considerable safety concerns due to its ...

The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine

Guizhou University of Traditional Chinese Medicine

Cancer pain is one of the most common and serious symptoms of cancer patients. At present, the agents used for the prevention or treatment of cancer pain do not act with optimal safety and efficacy. The nuclear factor kappa B (NF-κB) signaling pathway and its downstream inflammatory factors interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) play an important regulatory role in the developmental process of cancer pain. IKKβ is a key molecule of the IκB (IKK) kinase that propagates cellular responses to inflammation. Previous studies have shown that phosphorylation and degradation of the IκBα protein promotes the activation of NF-κB and the expression of TNF-α, IL-1β, and IL-6, participating in the formation and development of cancer pain. Chanling Gao (CLG) is a compound preparation of traditional Chinese medicine. It contains specific functions, namely nourishing Yin, activating blood circulation and relieving pain and dysfunction syndrome. It is used in the treatment of a variety of pain disorders including cancer-induced bone pain (CIBP), which has a certain relief effect. However, its mechanism of action still remains unclear. In the present study, a rat model of tibia CIBP was successfully established using the Walker 256 breast cancer cell line. The IKKβ/NF-κB signaling pathway and its related factors TNF-α, IL-1β, and IL-6 were used as the entry points to explore the effect of CLG on CIBP and their possible mechanisms of action. The results indicated that CLG improved the body mass of the CIBP rat model and increased the pain threshold in rats. CLG significantly inhibited the degradation of IκBα and the levels of p-IκBα, p-IKKβ, and p-p65 NF-κB proteins in the spinal cord of CIBP rats, inhibiting the contents of TNF-α, IL-1β, and IL-6. Therefore, we conclude that the analgesic effect of CLG in this rat model of CIBP may be related to the inhibition of the IKKβ/NF-κB signaling pathway and the reduction of synthesis and release of TNF-α, IL-1β, and IL-6.

Chanling Gao Attenuates Bone Cancer Pain in Rats by the IKKβ/NF-κB Signaling Pathway.

Cancer vaccines represent among the most promising strategies in the battle against cancers. However, the clinical efficacy of current cancer vaccines is largely limited by the lack of optimized delivery systems to generate strong and persistent antitumor immune responses. Moreover, most cancer vaccines require multiple injections to boost the immune responses, leading to poor patient compliance. Controlled-release drug delivery systems are able to address these issues by presenting drugs in a controlled spatiotemporal manner, which allows co-delivery of multiple drugs, reduction of dosing frequency and avoidance of significant systemic toxicities. In this review, we outline the recent progress in cancer vaccines including subunit vaccines, genetic vaccines, dendritic cell-based vaccines, tumor cell-based vaccines and  vaccines. Furthermore, we highlight the efforts and challenges of controlled or sustained release drug delivery systems (e.g., microparticles, scaffolds, injectable gels, and microneedles) in ameliorating the safety, effectiveness and operability of cancer vaccines. Finally, we briefly discuss the correlations of vaccine release kinetics and the immune responses to enlighten the rational design of the next-generation platforms for cancer therapy.

Hitchhiking on Controlled-Release Drug Delivery Systems: Opportunities and Challenges for Cancer Vaccines.

The genus Piper, a member of the Piperaceae family, comprises >2000 species, of which many are well known to possess considerable economic and medicinal values. Lignans are essential ingredients and are rich in Piper plants. Although many phytochemical studies have reported many lignans identified from Piper plants, comprehensive research has not reviewed these compounds. Hence, the present review reports on natural lignans from the genus Piper and their pharmacological activities. At least 275 lignans have been discovered from the Piper genus until October 2022, including traditional lignans, neolignans, oxyneolignans, norlignans, secolignans, and polyneolignans, especially some neolignans and norlignans with novel and complex scaffolds. In addition, these lignans have been reported to show various pharmacological activities, such as antimicrobial, anti-inflammatory, neuroprotective, antioxidative, anti-platelet aggregation, cytotoxic, anti-parasitic, CYP3A4 inhibitory activities, and so on. The current work presents an up-to-date critical review and a systematic summary of publications on lignans from the genus Piper to lay the groundwork and show better insights for further investigations.

Lignans from the genus Piper L. and their pharmacological activities: An updated review.

Rheumatoid arthritis (RA) is a major chronic autoimmune disease. Current conventional drugs face significant challenges, including severe side effects, high recurrence rates, and unsuitability for long-term use. In contrast, traditional Chinese medicine (TCM) has garnered increasing attention due to its multi-target regulatory advantages. Guan Jie Ke Be Wan (GJKBW) demonstrates notable therapeutic efficacy, but its therapeutic material basis and mechanisms of action remain unclear, which limits its precise clinical application and therapeutic optimization. Based on this, this study adopted Chinmedomics combined with Limited Proteolysis-coupled Mass Spectrometry (LIP-MS) molecular fishing technology to screen the key metabolic pathways in RA and analyze the relevant protein targets in these pathways. Key protein targets were extracted to identify the potential therapeutic material basis of GJKBW. LIP-MS and molecular dynamics analysis were employed to validate the reliability of its specific binding to the target proteins, and finalized the results and related mechanisms. Finally, the linoleic acid metabolic pathway was identified as a key pathway in RA. It was discovered that GJKBW exerted its therapeutic effects by targeting key proteins such as FADS2, PLA2G4A, and PLA2G15 to regulate linoleic acid metabolism. This regulation subsequently influenced the downstream metabolism of arachidonic acid, ultimately leading to the inhibition of the expression of related inflammatory factors. Isobergapten and Wogonin are identified as the therapeutic material basis for GJKBW within this mechanism of action. This study provides a novel paradigm for the "quantity-effect" correlation research of TCM formulas, incorporating "bioinformatics prediction-multi-omics validation-LIP-MS screening-molecular dynamics analysis".

Study of GJKBW against RA based on the Chinmedomics combined LIP-MS molecular fishing technology: A new strategy for discovering the therapeutic material basis.

Article	Year
Chanling Gao Attenuates Bone Cancer Pain in Rats by the IKKβ/NF-κB Signaling Pathway. Frontiers in pharmacology\| PubMed ID: 32431607	2020
Hitchhiking on Controlled-Release Drug Delivery Systems: Opportunities and Challenges for Cancer Vaccines. Frontiers in pharmacology\| PubMed ID: 34040536	2021
Lignans from the genus Piper L. and their pharmacological activities: An updated review. Fitoterapia\| PubMed ID: 36577457	2023
Study of GJKBW against RA based on the Chinmedomics combined LIP-MS molecular fishing technology: A new strategy for discovering the therapeutic material basis. Journal of pharmaceutical and biomedical analysis\| PubMed ID: 41875839	2026

Jinghua Ruan

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