Phytomedicine最新文献

Background: Severe liver fibrosis may be accompanied by intestinal barrier damage, such as bacterial peritonitis, suggesting that the role of the gut-liver axis is nonnegligible. Dachengqi decoction (DCQD) was reported to improve bowel movements, but whether DCQD was effective for intestinal damage caused by liver fibrosis remained unclear.

Purpose: To investigate the role of DCQD in liver fibrosis-related gut vascular barrier (GVB) damage in mice.

Study design: DCQD was verified to reduce the imbalance of the intestinal vascular barrier and restore intestinal homeostasis to prove that DCQD acts through the gut-liver axis.

Methods: Three graded doses of DCQD were gavaged into the CCL₄-induced mice for 12 weeks to evaluate the resistance to liver and intestinal damage. Immunoblotting and primary flow cytometry were used to assess organ damage; PV-1 to indicate gut vascular barrier damage; serum endotoxin, fecal SCFAs, and liver microbiota translocation to examine the gut-liver axis's crosstalk. Network pharmacology and RNA sequencing were used to analyze and verify the signaling pathway of DCQD.

Results: DCQD significantly ameliorated fibrosis and inflammatory response in the CCL₄-induced mice, alleviated gut leakage, downregulated PV-1, relieved liver enterobacterial translocation, restored intestinal homeostasis, and reduced infiltration of myeloid cells in the lamina propria. Network pharmacology and RNA sequencing results indicated that DCQD exerted anti-fibrotic and anti-inflammatory effects in the liver through inhibition of the ESR1/NF-κB/TNFα pathway and maintained GVB homeostasis through the FUT2/Wnt/β-Catenin pathway.

Conclusions: DCQD broke the closed-loop damage of the gut-liver axis to improve GVB injury in mice with liver fibrosis.

Background: Diarrhea and intestinal dysfunction commonly occur in young mammals, causing malnutrition and growth retardation in both human and livestock. As the traditional Chinese herb, mulberry leaf contains various bioactive compounds and showed several health benefits, such as regulating glucose and lipid metabolism, and modulating gut microbiota. Mulberry leaf exhibits the potential to modulate redox homeostasis and improve gut health, but the function and underlying mechanisms remains elucidative.

Purpose: To investigate the benefit of mulberry leaf on intestinal barrier in weanling pigs, illustrate the possible involvement of Keap1-Nrf2 mediated anti-oxidation and gut microbiota.

Methods: Chemical compositions of mulberry leaf powder (MLP) and mulberry leaf extract (MLE) were determined. The effects of MLP on growth performance, intestinal barrier integrity, anti-oxidative capacity, immune function and gut microbiota were evaluated in weaned pigs. The regulation of redox homeostasis by MLE and the involvement of Keap1-Nrf2 signaling were further determined in H₂O₂ induced oxidative stress (OS) model in IPEC-J2 cells via determining reactive oxygen species (ROS) production by flow cytometry and related protein abundance by western blot analysis.

Results: In weanling pigs, MLP reduced diarrhea incidence, and increased villus height, intestinal integrity and expression of tight junctions in intestinal mucosa. The improvement of intestinal barrier by MLP was associated with the enhancement in anti-oxidative capacity and the changes in gut microbiota and related short chain fatty acids production. Our study further revealed the direct regulation of MLE on tight junction expressions and ROS production to alleviate H₂O₂ induced OS in IPEC-J2 cells via the activating Keap1-Nrf2 signaling pathway.

Conclusions: Mulberry leaf in diet improved epithelial barrier via the direct anti-oxidation through the activation of Keap1-Nrf2 signaling pathway and the indirect modulation of gut microbiota in weaned pigs.

Background: Cardiac fibrosis plays a crucial role in the development of heart failure (HF) following myocardial infarction (MI). Endothelial-mesenchymal transition (EndMT) is one of the key drivers of cardiac fibrosis and subsequent cardiac dysfunction. The traditional Chinese medicine formula Bushen Huoxue Yiqi Formula (BHYF) is an effective prescription for treating HF, significantly improving cardiac function in patients. However, the underlying mechanisms of BHYF's efficacy remain inadequately understood.

Objective: This study aims to determine whether BHYF ameliorates HF by inhibiting cardiac fibrosis and to elucidate the intrinsic mechanisms involved.

Methods: A post-MI HF model was established by ligating the left anterior descending coronary artery in rats, and human umbilical vein endothelial cells (HUVEC) were stimulated with hypoxia/reoxygenation (H/R) in vitro. Active compounds in BHYF were identified using HPLC. Cardiac function and morphology were assessed using echocardiography, TTC staining, HE staining, Masson's trichrome, and Sirius Red staining. The mechanism of action of BHYF was evaluated using Western blotting, immunohistochemistry, and immunofluorescence.

Results: A total of 98 compounds, including glycosides, phenolic compounds, carboxylic acids, and others, were identified or preliminarily identified. BHYF improved cardiac function and myocardial damage in rats with MI-induced HF and mitigated cardiac fibrosis by inhibiting EndMT. Mechanistically, BHYF treatment inhibited EndMT by modulating the SIRT1/Notch1 pathway, thereby exerting anti-fibrotic effects in the heart.

Conclusion: Targeting EndMT based on the SIRT1/Notch1 pathway, BHYF may represent a novel antifibrotic therapeutic strategy, providing a scientific basis for the development of new cardiovascular drugs.

Background: Gastroesophageal reflux disease (GERD) is a chronic condition of the digestive tract with limited therapeutic options. Bitter taste receptors (TAS2Rs) and transient receptor potential vanilloid-1 (TRPV1) are implicated in modulating inflammatory responses. Berberine (BBR) and evodiamine (EVO) are known to activate TAS2Rs and TRPV1, respectively. However, whether BBR and EVO can ameliorate GERD by targeting TAS2Rs and TRPV1 remains uncertain.

Purpose: This study aims to determine whether BBR and EVO mitigate esophageal injury by targeting TAS2R38 and TRPV1 and to elucidate their underlying molecular mechanisms.

Methods: A GERD rat model was developed using esophagogastric anastomosis, while GERD in human esophageal epithelial cells (HEECs) was induced via bile acid (BA) exposure. Esophageal pathology was analyzed through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). mRNA and protein levels were measured via qRT-PCR, immunofluorescence, immunohistochemistry and Western blot analysis. Small interfering RNA was used to silence TAS2R38 and TRPV1 in HEECs. The activation of TAS2R38 and TRPV1 by BBR and EVO was assessed through Ca²⁺ mobilization assays. Finally, in vivo validation was conducted using U73122 to inhibit TAS2Rs and resiniferatoxin (RTX) to ablate TRPV1.

Results: BBR and EVO treatments significantly improved esophageal pathology in GERD rats and reduced BA-induced inflammation in HEECs. Additionally, BBR and EVO suppressed proinflammatory factors expression, upregulated barrier proteins such as E-cadherin and claudin-1, and inhibited the phosphorylation of p65, JNK, and ERK in the MAPK/NF-κB signaling pathways in both in vivo and in vitro models. Furthermore, BBR and EVO, whether individually or in combination, reduced dilated intercellular spaces (DIS), increased desmosome numbers, and modulated macrophage polarization in GERD rats. Knockdown of TAS2R38 and TRPV1 in HEECs notably diminished the stimulatory effects of BBR and EVO. Moreover, the regulation of barrier function and MAPK/NF-κB pathway proteins by BBR and EVO in BA-induced HEECs was abrogated upon TAS2R38 and TRPV1 knockdown. Similarly, U73122 and RTX reversed the effects of BBR and EVO on macrophage polarization and MAPK/NF-κB signaling pathways in vivo.

Conclusion: We firstly demonstrate that BBR and EVO alleviate GERD, with enhanced synergistic efficacy observed when used in combination. Mechanistically, BBR and EVO activate the TAS2R38 and TRPV1, respectively, leading to downregulation of phosphorylation in MAPK/NF-κB signaling pathways and modulation of macrophage polarization. These findings offer a novel foundation for the clinical application of BBR and EVO in GERD treatment.

Background: The genus Bauhinia and its species has been known since ages by tribal people and medicinal practitioners in tropical and subtropical regions for the treatment of diabetes, diarrhea, cough, fever, stomach disorders, skin diseases, and other diseases.

Study design: Our aim was to collect and explore the literature available on the traditional applications and medicinal potential of genus Bauhinia across Asia, so that this review can be used as standard to analyze the immense potential of this genus and can be explored further for clinical use.

Methods: The information was rigorously gathered from Google Scholar, Pub Med, Elsevier, Wiley Online Search, Science Direct, and other literature sources.

Results: As per the literature, this genus possesses antimicrobial, antioxidant, nephroprotective, anticancer, hepatoprotective, antidiabetic, anti-inflammatory, and antidepressant activities both in vitro and in vivo, due to the presence of flavonoids, steroidal saponins, bauhinioxepins, chromanones, and phenolic compounds.

Conclusion: In this review, we have detailed for the first time the categorized information about traditional uses, geographical distribution, morphological features, phytochemistry, pharmacological, and toxicological effects, and patents associated with Bauhinia species. However, more research is needed to explore the mechanisms of action, pharmacokinetics of the phytoconstituents, and clinical evaluation for their future use in treating various ailments.

Background: Triple-negative breast cancer (TNBC) recurrence and metastasis are the major causes of failure in TNBC therapy. The difficulties in treating TNBCs may be because of increased cancer cell plasticity that involves the fine-tuning of cellular redox homeostasis, mitochondrial bioenergetics, metabolic characteristics, and the development of cancer stem cells (CSCs).

Purpose: To investigate the effects and the underlying mechanisms of the phytosesquiterpene lactone deoxyelephantopin (DET) and its semi-synthesized derivative (DETD-35) in suppressing different phenotypic TNBC cell populations that contribute to tumor metastasis.

Methods: A timelapse microfluidic-based system was established to analyze the effects of DETD-35 and DET on cell migration behavior in an oxygen gradient. Seahorse real-time cell metabolic analyzer and gas chromatography/quadrupole-time-of-flight mass spectrometry (GC/Q-TOF MS) were utilized to analyze the effects of the compounds on mitochondrial bioenergetics in TNBC cells. A miRNA knockout technique and miRNA sponges were employed to evaluate the miR-4284 involvement in the anti-TNBC cell effect of either compound.

Results: DETD-35 and DET attenuated TNBC cell migration toward hypoxic regions under a 2-19 % oxygen gradient in a timelapse microfluidic-based system. DETD-35 and DET also suppressed CSC-like phenotypes, including the expression of Sox2, Oct4, and CD44 in TNBC cells under hypoxic conditions. DETD-35 and DET affected mitochondrial basal respiration, ATP production, proton leak, and primary metabolism, including glycolysis, the TCA cycle, and amino acid metabolism in the lung-metastatic TNBC cells. Furthermore, the expression of mitophagy markers PARKIN, BNIP3, PINK1, LC3-II, and apoptotic markers Bax, cleaved caspase 7, and cleaved PARP in hypoxic and lung-metastatic TNBC cells was also regulated by treatment with either compound. In miR-4284 knockout cells or miR-4284 inhibitor co-treated TNBC cells, DET- and DETD-35-induced over-expression of mitophagic and apoptotic markers was partially reversed, indicating miR-4284 involved with the compounds caused programmed cell death.

Conclusion: This study demonstrated the novel activities of DETD-35 and DET in suppressing CSC-like phenotypes and metastatic TNBC cells through the de-regulation of mitochondrial bioenergetics.

Background: Characterized by β-amyloid (Aβ) plaques, neurofibrillary tangles, and aberrant neuroinflammation in the brain, Alzheimer's disease (AD) is the most common neurodegenerative disease. Microglial polarization is a subtle mechanism which maintains immunological homeostasis and has emerged as a putative therapeutic to combat AD. Berberine (BBR) is a natural alkaloid compound with multiple pharmacological effects, and has shown considerable therapeutic potential against inflammatory disorders. However, BBR functions and underlying mechanisms in neuroinflammation remain unclear.

Purpose: To examine BBR pharmacological effects and mechanisms in neuroinflammation with a view to treating AD.

Methods: BBR effects on cognitive performance in 5 × FAD mice were assessed using open field, Y-maze, and Morris Water Maze (MWM) tests. Neuroinflammation-related markers and Aβ pathology were examined in brain sections from mice. Transcriptomic analyses of hippocampus tissues were also conducted. Microglial BV2 cells were also used to verify potential BBR mechanisms in neuroinflammation and microglial polarization.

Results: BBR improved cognitive performance, reduced amyloid pathology, and alleviated aberrant neuroinflammation in an AD mouse model. BBR induced microglial polarization to an M2-like phenotype, which was manifested by lowered and elevated proinflammatory and anti-inflammatory cytokine production, respectively, improved microglial uptake and Aβ clearance. Mechanistically, BBR directly interacted with TYROBP and promoted its activation by stabilizing TYROBP oligomerization. TYROBP knockdown aggravated M1-like polarization and pro-inflammatory gene expression in microglial cells in the presence of lipopolysaccharide (LPS)+Aβ, while blocked microglial M2-like polarization benefited from BBR administration.

Conclusions: BBR modulated neuroinflammation by regulating microglial polarization via TYROBP activation. Our study provided new insight into BBR pharmacological actions in regulating microglial homeostasis and combating AD.