BMC Complementary Medicine and Therapies最新文献

The spreading of COVID-19 has posed a risk to global health, especially for lung cancer patients. An investigation is needed to overcome the challenges of COVID-19 pathophysiology and lung cancer disease. This study was designed to evaluate the phytoconstituents in Punica granatum peel (PGP), its anti-lung cancer activity, and in silico evaluation for antiviral potential. GC-MS technique was used to detect the phytoconstituents. Cytotoxicity was analyzed using MTT dye, followed by apoptosis, ROS generation, and cell cycle phase detection in human lung cancer cells (A549). The glide module of Maestro software was used to investigate the molecular-docking interaction of the constituents against main protease (Mpro) and papain-like protease (PLpro) of SARS-CoV-2. GROMACS 2023.2 was utilized to evaluate the complex stability. A total of nineteen phytocomponents were detected in the PGP extract through GC-MS analysis. PGP has shown a potential to reduce lung cancer cell proliferation while evading normal cell death. PGP induced apoptosis by arresting cells in the G0/G1 phase and generating ROS. A total of six and eight phytocomponents had a high affinity for PLpro and Mpro proteins, respectively. The top docked complex, ethyl 5-oxo-2-pyrrolidinecarboxylate, with PLpro and Mpro proteins, showed likely stable interaction throughout 100 ns simulation. This finding raises the possibility of top-eight hits (docking score ≥ -1.0 kcal/mol) preventing SARS-CoV-2 severity. The phytoconstituents exhibited orally active drugs with no more than one violation and drug-likeness activity. The PGP phytoconstituents are suggested to be dual agents for lung cancer and SARS-CoV-2 pathogenesis.

Background: It seems that oxidative stress is involved in the occurrence and progression of non-alcoholic fatty liver disease (NAFLD). Considering the antioxidant features of Ellagic acid (EA), this study was designed to assess the effect of EA on some biochemical factors in patients with NAFLD.

Methods: In this clinical trial, 44 patients were selected based on including criteria and randomly received 180 mg of EA per day (n = 22) or placebo (n = 22) for 8 weeks. At the beginning and end of the study, glycemic indices, lipid profiles, liver enzymes, oxidative stress markers, and inflammatory factors were measured.

Results: At the end of the study, the mean of insulin, insulin resistance (IR), triglycerides (TG), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), malondialdehyde (MDA), and C-reactive protein (CRP) were significantly decreased in the intervention group (P < 0.05). Also, a significant increase in the mean of total antioxidant capacity (TAC) was observed in the EA group (P < 0.05). However, changes in high-density lipoprotein (HDL), total cholesterol (TC), and fasting blood sugar (FBS) were not significant in any of the groups (P > 0.05).

Conclusions: Based on the results, the present study provided evidence that EA can be used as a supplemental therapy alongside current treatment plans to reduce the complications of NAFLD due to its antioxidant and anti-inflammatory properties.

Trial registration: This study was prospectively registered at the Iranian Registry of Clinical Trials on the 23th of January 2022 (ID: IRCT20141025019669N21).

Background: Suhexiang (SHX) pill is widely used for treating acute ischemic stroke (AIS). Experimental and randomized controlled trials suggested that SHX pill was beneficial for patients with AIS. However, the effectiveness of SHX pill in real-world practice setting remains unclear. It is of great importance to investigate the effectiveness and safety of SHX pill in patients with acute ischemic stroke in real-world clinical practice with long-term follow-up.

Methods: The Suhexiang pill for acute ischemic stroke in Real-world Practice Setting (SUNRISE) is a multicenter, prospective, product-specific, observational study designed to provide insight into the administration of SHX pill for patients with AIS in the real-world clinical practice setting, with an initial sample size of 1000. Eligible patients treated with SHX pill within seven days of AIS onset will be consecutively included in this registry. The primary outcome is the proportion of patients independent at 3 months after stroke onset defined by an mRS score of 0, 1, or 2.

Conclusion: The findings of the SUNRISE registry will not only provide insights into the characteristics of patients who may benefit from SHX treatment, but also may enable the individualized treatment decision-making of SHX pill in real-world practice setting.

Study registration: This study was registered with the ClinicalTrials.gov (URL: https://clinicaltrials.gov/ , Unique identifier: NCT05833932).

Duranta erecta Linn. belongs to the Verbenaceae family and is primarily found in subtropical, tropical, and temperate climates. The plant has been reported to contain a variety of phytoconstituents, including iridoid glycosides, flavonoids, flavonoid glycosides, alkaloids, phenolics, tannins, terpenoids, steroids, and saponins. In this investigation, a bioactivity-guided isolation was used to isolate cyclooxygenases (COXs) and lipoxygenase (LOX)-inhibiting compounds from the leaves of Duranta erecta Linn. Duranterectoside A (1), lamiide (2), and apigenin 4',7-dimethyl ether (3) were identified employing spectroscopic methods (including ESI-MS, ¹H-NMR, and ¹³C-NMR), and by comparing with existing literature data. This is the first report of metabolitrs from D. erecta inhibiting both LOX and COX enzymes. Furthermore, the isolated compounds were analyzed using computerized virtual screening, which enabled the modelling ADME characteristics, molecular docking, and dynamics simulation. The results demonstrated that compound 1 had greater docking scores than the docked lead compounds. Overall, the data reported in this study add to our understanding of the pharmacological properties of the examined plant and Duranterectoside A (1) and pave the way for future research and investigation in inflammation and drug discovery.

Background: Atherosclerosis serves as the fundamental pathology for a variety of cardiovascular disorders, with its pathogenesis being closely tied to the complex interplay among lipid metabolism, oxidative stress, and inflammation. Wogonoside is a natural flavonoid extracted from Scutellaria baicalensis with a variety of biological activities, including anti-inflammatory, hypolipidemic, and cardiac function improvement properties. Despite these known effects, the specific role of wogonoside in the context of atherosclerosis remains to be elucidated.

Purpose: To validate the efficacy of wogonoside in the treatment of atherosclerosis and to investigate its possible therapeutic mechanisms.

Methods: Network pharmacology was used to obtain the core targets and signaling pathways that may be efficacious in the treatment of atherosclerosis with wogonoside, which were validated using molecular docking and molecular dynamics simulations. To further validate the core targets in the signaling pathway, we performed in vivo experiments using apolipoprotein E (ApoE)-/- mice. This included pathological morphology and lipid deposition analysis of mouse aorta, serum lipid level analysis, Elisa analysis, oxidative stress analysis, reactive oxygen species (ROS) fluorescence assay, immunohistochemical analysis and protein blot analysis.

Results: Predictions were obtained that wogonoside treatment of atherosclerosis has 31 core targets, which are mainly focused on pathways such as Toll-like receptor (TLR) signaling pathway and NF-kappa B (NF-κB ) signaling pathway. Molecular docking and molecular dynamics simulations showed that wogonoside has good binding properties to the core targets. In vivo experimental results showed that wogonoside significantly inhibited aortic inflammatory response and lipid deposition, significantly reduced the release levels of total cholesterol (TC), triglycerides (TG), low-density-lipoprotein cholesterol (LDL-C), oxidized low density (ox-LDL) and free fatty acid (FFA), and significantly inhibited the release of inflammatory factors TNF-α, IL-1β, IL-6 and oxidative stress in ApoE-/- mice. Further molecular mechanism studies showed that wogonoside significantly inhibited the activation of TLR4/NF-κB signaling pathway in ApoE-/- mice.

Conclusion: Wogonoside may be an effective drug monomer for the treatment of atherosclerosis, and its mechanism of action is closely related to the inhibition of the activation of the TLR4/NF-κB signaling pathway.

Background: Amorpha fruticosa was used for treating burn, ambustion, carbuncle, and eczema in the traditional Chinese medicine. Although more and more attention has been paid to its biological activity recently, the antitumor activities of the essential oils (EOs) extracted from its leaves (AFLEO) and flowers (AFFEO), and their molecular mechanisms have never been reported up to now. The objective of present study was to examine the chemical compositions of AFLEO and AFFEO, then investigate the effects and pharmacological mechanism of EOs against hepatocellular carcinoma (HCC).

Methods: The chemical compositions of EOs were examined using gas chromatography-mass spectrometry (GC-MS). The inhibitory effect of the EOs on HCC was evaluated by MTT assay. The detected components of AFLEO and AFFEO were performed ADME screening to examine their drug-likeness. Then a PPI network, compound-target network, compound-target-pathway network, gene ontology, and KEGG enrichment for HCC were applied to identify the targets and pathways for AFLEO and AFFEO against HCC. Molecular docking of the main components and their targets was performed to predict the binding affinity. Western blotting was used to verify the results.

Results: 30 components were identified from AFLEO, while 22 components from AFFEO. Both AFLEO and AFFEO inhibited the proliferation of HCC cells in a time and dose-dependent manner. 10 compounds of AFLEO and 9 compounds of AFFEO were screened out for further analysis. 28 hub targets of AFLEO and 40 hub targets of AFFEO were detected by PPI network. KEGG analysis revealed that pathways in cancer, chemical carcinogenesis - receptor activation and proteoglycans in cancer were related to the EOs against HCC. Molecular docking confirmed that the main component of the EOs has high affinity to the targets of HCC.

Conclusions: AFLEO and AFFEO may suppress HCC by acting on multiple targets and regulating multiple pathways.

Background: Oral squamous cell carcinoma (OSCC) ranks as the sixth most common malignancy globally. Cisplatin is the standard chemotherapy for OSCC, but resistance often reduces its efficacy, necessitating new treatments with fewer side effects. Rumex dentatus L., from the Polygonaceae family, is known for its medicinal properties, but its anticancer potential has not been thoroughly explored. This study aimed to investigate the synergy between cisplatin and an extract from the aerial parts of R. dentatus L. in treating tongue carcinoma (HNO97) in vitro, using network pharmacology, biological verification, and phytochemical analysis.

Methods: The study included UPLC-ESI-MS/MS analysis, cytotoxicity assays, cell cycle analysis, apoptosis assessment, and RT-qPCR for gene expression of Bcl2, p53, and ATG7. Potential targets were identified, and mechanisms of action were examined through online databases and enrichment analyses.

Results: The R. dentatus L. extract contained 14 phenolic aglycons. Combining cisplatin and R. dentatus L. was more effective in inhibiting proliferation, inducing cell cycle arrest and apoptosis, and reducing autophagy in HNO97 cells than cisplatin alone. KEGG analysis indicated that the drug combination might work through pathways like PI3K-Akt signaling, microRNAs in cancer, and EGFR tyrosine kinase inhibitor resistance.

Conclusions: Combining cisplatin with R. dentatus L. may be a promising approach for treating tongue carcinoma by affecting multiple pathways, providing a new perspective for developing more effective treatments for OSCC.

Heart failure (HF) is a complex syndrome marked by considerable expenditures and elevated mortality and morbidity rates globally. Shenmai injection (SMI), a form of Traditional Chinese Medicine-based therapy, has demonstrated effectiveness in treating HF. Recent research suggests that Traditional Chinese Medicine (TCM) may induce beneficial changes in microbial-host co-metabolism, potentially providing cardiovascular protection. This study used a rat model of hypertensive heart failure (H-HF) to explore the mechanism of SMI. The possible compounds and key targets of SMI against H-HF were investigated using network pharmacology. The pharmacodynamics of SMI were validated using the H-HF animal model, with analysis of fecal gut microbiota integrating metabolomics and 16S rRNA sequencing. Metorigin metabolite traceability analysis and the MetaboAnalyst platform were utilized to explore the action mechanism. To evaluate changes in serum TMAO levels, targeted metabolomics was performed. Finally, the study looked at the intrinsic relationships among modifications in the intestinal flora, metabolite profile changes, and the targets of SMI compounds to clarify how they might be used to treat H-HF. According to metabolomics and 16S rRNA sequencing, by reestablishing homeostasis in the gut microbiota, SMI affects vital metabolic pathways, such as energy metabolism, amino acid metabolism, and bile acid metabolism. Increased serum TMAO levels were identified to be a risk factor for H-HF, and SMI was able to downregulate the levels of TMAO-related metabolites. Network pharmacology analysis identified 13 active components of SMI targeting 46 proteins, resulting in differential expression changes in 8 metabolites and 24 gut microbes. In conclusion, this study highlights the effectiveness of SMI in alleviating H-HF and its potential to modulate microbial-host co-metabolism. Through a comprehensive discussion of the interconnected relationships among the components, targets, metabolites, and gut microbiota, it provided fresh light on the therapeutic mechanism of SMI on H-HF.