Wenjing decoction: Mechanism in the treatment of dysmenorrhea with blood stasis syndrome through network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) formula Wenjing Decoction (WJD) longstanding efficacy in enhancing blood circulation, resolving blood stasis, and mitigating dysmenorrhea symptoms. Despite its prevalent application, the specific mechanism underlying effect of WJD remains elusive. OBJECTIVE: The purpose of this study is to examine the material basis of Wenjing Decoction and explore the effect of WJD on rat models of dysmenorrhea with blood stasis syndrome and elucidate its mechanism. METHODS: In this study, we initially identified the chemical constituents of WJD using liquid chromatography-mass spectrometry (LC-MS). Subsequently, we employed network pharmacology to predict the mechanism of WJD in treating acute blood stasis dysmenorrhea. To further investigate the role of WJD, we established a rat model of acute blood stasis. We monitored changes in blood coagulation indexes, IL-6, TNF-α, NO, and COX-2 in rats before and after administration to confirm the successful establishment of the rat model and evaluate the therapeutic effect of WJD on dysmenorrhea and acute blood stasis. Finally, real-time fluorescence quantitative PCR (qPCR) and Western blot (WB) were utilized to investigate its mechanism. RESULTS: Through LC-MS analysis, 69 chemical substances were identified in WJD. Network pharmacology study revealed that the mechanism of WJD in treating BSS may be associated with the PI3K/AKT/NF-κB pathway. Following administration, the WJD group showed gradual recovery of physical signs and coagulation index to a healthy level. Additionally, the levels of IL-6, TNF-α, and COX-2 decreased in a dose-dependent manner, whereas NO levels increased. Results from QPCR and WB detection indicated increased expression levels of p-PI3K, p-AKT, Bcl-2, and eNOS, and decreased expression levels of Bax, NFκBp65, ICAM1, and VCAM1. CONCLUSION: The results show that WJD significantly improves the characterization, dysmenorrhea index, and coagulation-related factors in BSS rats. Through network pharmacological prediction, real-time fluorescence quantitative PCR, and Western blot analysis, it is postulated that the beneficial effects of WJD on dysmenorrhea may be linked to the PI3K/AKT/NF-κB signaling pathway. These findings offer a theoretical foundation for the advancement and utilization of WJD.

Evaluation of comparative chemical profiling and bioactivities of medicinal and non-medicinal parts of Ampelopsis delavayana.

Ampelopsis delavayana, a distinctive Yi medicine, utilized the roots as an essential medicinal substance for trauma treatment of the "Yunnan Hong Yao". A. delavayana, however, cannot be cultivated artificially presently, and it has been described with a phenomenon of mixed utilization of roots and stems, impeding pharmaceutical quality control. In response to resource scarcity and standardization issues, the research comprehensively compares the material basis and efficacy of medicinal (roots) and non-medicinal (stems) parts by using chemical profiling and pharmacological methodologies. Chemical disparity between two parts was compared by TLC and HPLC. Analgesia and anti-inflammatory capabilities of both parts were comprehensively evaluated through acetic acid writhing test, hot plate test, and xylene-induced mouse ear swelling test. Additionally, all the extracts were evaluated for anti-inflammatory activities by monitoring regulation of the levels of TNF-α, IL-1ß, IL-6, and IgE in ear tissue. Consequently, the findings of TLC and HPLC revealed substantial similarity in the material basis of the medicinal and non-medicinal parts of A. delavayana, and pharmacological activities of anti-inflammatory and analgesic between two parts were consistent. Different extracts remarkably reduced the levels of TNF-α, IL-1ß, IL-6, and IgE, demonstrating no discernible differences. Collectively, the comprehensive exploitation indicated that the medicinal and non-medicinal parts of A. delavayana exhibited identical chemical profiling and bioactivities, providing a theoretical rationale and scientific evidence for using stems as a therapeutic part, thereby holding considerable potential for ameliorating the current status of its medicinal reserves.

Mechanism of action of Taohong Siwu decoction in the alleviation of primary dysmenorrhea.

Background: As one of the most common gynecological disorders, PD significantly impacts the quality of life for women. TSD, a well-known traditional Chinese medical prescription, has gained popularity for its use in treating gynecological cold coagulation and blood stasis syndromes such as PD. However, the lack of comprehensive data hinders our understanding of its molecular mechanism. Purpose: The objective of the present study is to investigate the therapeutic effects of TSD on PD and elucidate its plausible mechanism. Methods: HPLC was employed to confirm the presence of the principal metabolites of TSD. The rat model of PD was induced by OT exposure following IWM and EB pretreatment, and subsequently treated with TSD via gastric gavage. The effects and potential mechanisms of TSD on PD rats were explored, encompassing general behavior, morphological alterations in the uterus and ovaries, biochemical indicators in the uterus and serum, and levels of proteins related to the PI3K/AKT signaling pathway. Results: Gallic acid, hydroxysafflower yellow A, albiflorin, paeoniflorin, and ferulic acid were determined to be the primary active metabolites of TSD. The pharmacological studies yielded results indicating the successful establishment of the PD model in rats. Additionally, TSD demonstrated its ability to protect PD rats by ameliorating general behavior, mitigating pathological damage to uterine and ovarian tissues, and modulating the expression levels of correlated factors (PGE2, PGF2α, Ca2+, TXB2, IL-6, TNF-α, NO, and COX-2) as well as p-PI3K/PI3K and p-AKT/AKT proteins. Conclusion: TSD exhibited protective effects against PD in rats through its interaction with multiple targets including P13K/AKT signaling pathway, indicating that TSD holds therapeutic potential for PD treatment and providing evidence supporting the rational utilization of TSD.

Integrating multi-level interactive network and in vivo/vitro studies to explore the protective mechanism of Ampelopsis grossedentata in hyperuricemia.

The strategies or drugs for preventing and treating Hyperuricemia (HUA) are still lacking. As a traditional Chinese medicine (TCM) with a profound history, Ampelopsis grossedentata has been shown to play diverse biological roles. The purpose of the present study was to evaluate hypouricemic effect of A. grossedentata, and investigate its involved material basis and mechanism. A HUA mice model was established to evaluate the therapeutic effects of A. grossedentata. And then some extracts from A. grossedentata were prepared, isolated and analyzed. Furthermore, network pharmacology, based on the above results, was used to discover potential active ingredients and therapeutic targets, and they were further verified and explored by molecular docking and in vitro experiments. In vivo experiments showed that A. grossedentata exerted hypouricemic effect on mice of HUA. The core active ingredients (quercetin, myricetin and dihydromyricetin etc.) and core targets (PTGS2, XOD and ABCG2 etc.) for A. grossedentata to treat HUA were predicted by network pharmacology. And molecular docking showed that the spontaneous binding activities of above components and targets were marvelous. In vitro experiments further demonstrated that A. grossedentata exerted hypouricemic effect by decreasing the levels of UA, XOD, antioxidant factors, inflammatory factors, GLUT9 and URAT1 in HK-2 cells of HUA. Taken together, this study integrates multi-level interaction network with in vivo/vitro experiments to systematically reveal the material basis and mechanism of A. grossedentata in treating HUA, which provides a scientific basis for further study of A. grossedentata and HUA.

Anti-inflammatory and analgesic effects of Streblus indicus.

The bark of Streblus indicus, a Dai medicine in China, has been listed in the Chinese Materia Medica as possessing hemostatic and analgesic properties. Ethnic medicine books record that its bark or leaves for the treatment of mumps and lymphoma. However, according to the literature survey, anti-inflammatory and analgesic studies available for leaves and branches of S. indicus have been seldom reported so far. The current study focuses on the metabolites of S. indicus bark and leaves responsible for anti-inflammatory and analgesic effects on the basis of bioactive-included acetic acid writhing, hot-plate, and xylene-induced ear swelling. The secretion of inflammatory mediators, TNF-α, IL-6, IL-1ß, IL-4, and IL-10, were evaluated for their anti-inflammatory by xylene-induced in mouse ear cells. Histological examination was used to assess the anti-inflammatory and analgesic effects of the branches and leaves of S. indicus, and Western blot analysis determined the mechanism of the methanolic extract of branches and leaves. Different metabolites of S. indicus significantly alleviated analgesic and anti-inflammatory effects, with no discernable differences among them. All metabolites decreased the levels of TNF-α, IL-1ß, and IL-6 and increased the levels of IL-4 and IL-10. The analgesic and anti-inflammatory mechanism of the methanolic extract was related to the NF-kB signaling pathway. These results not only would account for scientific knowledge for the traditional application of S. indicus, but also provide a credible theoretical foundation for the further development of anti-inflammatory and analgesic agents.

Swertiamarin or heat-transformed products alleviated APAP-induced hepatotoxicity via modulation of apoptotic and Nrf-2/NF-κB pathways.

Objective: Swertiamarin (STM) belongs to iridoid class of compounds, and the heat-transformed products (HTPS) are produced by STM in the process of drug processing. The purpose of this study was to explore the protective effect and mechanism of STM or HTPS on acetaminophen (APAP)-induced hepatotoxicity. Methods: Mice and L-O2 cells were given APAP to establish the hepatotoxicity model in vivo and in vitro. The effects of STM or HTPS on oxidative stress, inflammation, and apoptosis induced by APAP were evaluated, with N-acetylcysteine (NAC) as a positive control. Results: STM or HTPS reduced the APAP-induced apoptosis of L-O2 cells and significantly alleviated the liver injury index induced by APAP (p < 0.01, 0.005) Interestingly, HTPS had better protective effect against APAP-induced hepatotoxicity than STM (p < 0.05). In addition STM or HTPS improved the histological abnormalities; inhibited lipid peroxidation and reduced the level of inflammatory mediators. They also activated the defense system of nuclear factor erythroid 2 related factor 2 (Nrf-2) and inhibited nuclear factor-κ B (NF-κB).

(±)-Zanthonitidumines A and B: Two new benzophenanthridine alkaloids enantiomers from Zanthoxylum nitidum and their anti-inflammatory activity.

Two new benzophenanthridine alkaloids enantiomers (±)-zanthonitidumines A (1) and B (2), along with seven known analogues (3-9), were isolated from Zanthoxylum nitidium. Their structures were elucidated on the basis of extensive spectroscopic techniques and ECD data. Compound 2 exhibited the most significant inhibition of IL-6 generation as well as TNF-α release which suggest that it may be a potential anti-inflammatory agent.