Epigallocatechin-3-gallate mitigates cadmium-induced intestinal damage through modulation of the microbiota-tryptophan-aryl hydrocarbon receptor pathway.

Early studies have shown that the gut microbiota is a critical target during cadmium exposure. The prebiotic activity of epigallocatechin-3-gallate (EGCG) plays an essential role in treating intestinal inflammation and damage. However, the exact intestinal barrier protection mechanism of EGCG against cadmium exposure remains unclear. In this experiment, four-week-old mice were exposed to cadmium (5 mg kg-1) for four weeks. Through 16 S rDNA analysis, we found that cadmium disrupted the gut microbiota and inhibited the indole metabolism pathway of tryptophan (TRP), which serves as the principal microbial production route for endogenous ligands to activate the aryl hydrocarbon receptor (AhR). Additionally, cadmium downregulated the intestinal AhR signaling pathway and harmed the intestinal barrier function. Treatment with EGCG (20 mg kg-1) and the AhR agonist 6-Formylindolo[3,2-b] carbazole (FICZ) (1 µg/d) significantly activated the AhR pathway and alleviated intestinal barrier injury. Notably, EGCG partially restored the gut microbiota and upregulated the TRP-indole metabolism pathway to increase the level of indole-related AhR agonists. Our findings demonstrate that cadmium dysregulates common gut microbiota to disrupt TRP metabolism, impairing the AhR signaling pathway and intestinal barrier. EGCG reduces cadmium-induced intestinal functional impairment by intervening in the intestinal microbiota to metabolize AhR agonists. This study offers insights into the toxic mechanisms of environmental cadmium and a potential mechanism to protect the intestinal barrier with EGCG.

Dihydromyricetin Nanoparticles Alleviate Lipopolysaccharide-Induced Acute Kidney Injury by Decreasing Inflammation and Cell Apoptosis via the TLR4/NF-κB Pathway.

Acute kidney injury (AKI) is the most severe and fatal complication of sepsis resulting from infectious trauma. Currently, effective treatment options are still lacking. Dihydromyricetin is the main component extracted from Vine tea (Ampelopsis megalophylla Diels et Gilg). In our previous research, chitosan-tripolyphosphate-encapsulated nanoparticles of dihydromyricetin (CS-DMY-NPs) have been proven to have potential protective effects against cisplatin-induced AKI. Here, we investigated the protective effects and mechanisms of DMY and its nano-formulations against LPS-induced AKI by assessing pathological and inflammatory changes in mice. In mice with LPS-AKI treated with 300 mg/kg CS-DMY-NPs, the levels of creatinine (Cr), blood urea nitrogen (BUN), and KIM-1 were significantly reduced by 56%, 49%, and 88%, respectively. CS-DMY-NPs can upregulate the levels of GSH, SOD, and CAT by 47%, 7%, and 14%, respectively, to inhibit LPS-induced oxidative stress. Moreover, CS-DMY-NPs decreased the levels of IL-6, IL-1ß, and MCP-1 by 31%, 49%, and 35%, respectively, to alleviate the inflammatory response. TUNEL and immunohistochemistry showed that CS-DMY-NPs reduced the number of apoptotic cells, increased the Bcl-2/Bax ratio by 30%, and attenuated renal cell apoptosis. Western blot analysis of renal tissue indicated that CS-DMY-NPs inhibited TLR4 expression and downregulated the phosphorylation of NF-κB p65 and IκBα. In summary, DMY prevented LPS-induced AKI by increasing antioxidant capacity, reducing inflammatory responses, and blocking apoptosis, and DMY nanoparticles were shown to have a better protective effect for future applications.

The antivirulence activity, transcriptomics of EGCG and its protective effects on zebrafish infected by Aeromonas hydrophila.

Background: Aeromonas hydrophila is an important pathogen that mainly harms aquatic animals and exhibits resistance to a variety of antibiotics. This study investigated the effect of epigallocatechin-3-gallate (EGCG) on the virulence factors of A.hydrophila and its impact on adhesion, invasion, and cytotoxicity in Caco-2 cells. The potential mechanism of antibacterial activity of EGCG was investigated by transcriptomic analysis. Results: EGCG not only inhibited the production of biofilm, hemolytic activity, motility, and protease activity of A.hydrophila, but also reduced its adhesion, invasion, and cytotoxicity in Caco-2 cells. Transcriptomic analysis indicated that the antimicrobial activity of EGCG may be achieved by weakening the chemotaxis and stress response of the bacteria, as well as inhibiting the TonB system. Animal studies demonstrated that EGCG can significantly improve the survival rate and organs damage of zebrafish infected with A.hydrophila. Conclusion: EGCG would be a potential alternative drug for the prevention and treatment of A. hydrophila infections by anti-virulence mechanism.

Preparation, characterization and protective effect of chitosan - Tripolyphosphate encapsulated dihydromyricetin nanoparticles on acute kidney injury caused by cisplatin.

Dihydromyricetin (DMY) is a natural dihydroflavonol compound known for its diverse pharmacological benefits. However, its limited stability and bioavailability posed significant challenges for further applications. To address these issues, in this study, an ion crosslinking method was utilized to prepare chitosan nanoparticles that were loaded with DMY. The synthesized chitosan nanoparticles (CS-DMY-NPs) were spherical in shape with particle size and ζ potential of 198.7 nm and 45.05 mV, respectively. Furthermore, in vitro release experiments demonstrated that CS-DMY-NPs had sustained release and protective effects in simulated gastric and intestinal fluids. CS-DMY-NPs exhibited better antioxidant activity by ABTS and DPPH radical scavenging activity than free DMY. In vivo study showed that CS-DMY-NPs alleviated cisplatin-induced kidney damage by inhibiting oxidative stress and proinflammatory cytokines, and had better activity compared to DMY (free). Immunofluorescence data showed that CS-DMY-NPs activated the Nrf2 signaling pathways in a dose-dependent manner to combat cisplatin-induced kidney damage. Our results demonstrate that CS-TPP has good compatibility with DMY, and CS-DMY-NPs exhibited better protective effects against cisplatin-induced acute kidney injury (AKI) than free DMY.

Image Analysis of TVCDS in Infertile Patients with Polycystic Ovary Syndrome.

In order to analyze and examine the TVCDS images of infertile patients, this paper conducted an in-depth study based on the symptoms of polycystic ovary syndrome. Through the sample size estimation method, mathematical analysis, and other methods, the image examination of the polycystic ovary in TVCDS was successfully analyzed. 86 cases of infertile patients with PCS were divided into a control group treated with clomiphene alone and an observation group treated with clomiphene combined with TCM periodic therapy, with 43 patients in each group. The therapeutic effects of the two groups were compared and analyzed. Results show that the treatment effective rate and pregnancy success rate of the observation group were 95.35% and 88.37%, respectively, and those of the control group were 83.72% and 76.74%, respectively. The difference between the two groups was statistically significant (P < 0.05). It was understood that the main pathogenesis of polycystic ovary syndrome is the abnormal balance of kidney, qi, and blood meridians. Thus, the balance of kidney-anemone-chong Ren-uprisal is broken and the result is infertility symptoms or irregular menstruation. After a study on TVCDS in infertile patients, it was observed that the levels of progesterone (P) and luteinizing hormone (LH) in patients with irregular menstruation were significantly increased. The increase was higher than that in the control group, with an overall negative rate of 4.00%, compared with 18.00% of the control group, showing a significant difference. It also indicates that TVCDS image examination has a very significant effect on improving menstrual irregularities and reducing the incidence of adverse reactions.

Enhancement of the functionality of attenuating acute lung injury by a microemulsion formulation with volatile oil of Angelicae Sinensis Radix and Ligusticum Chuanxiong Rhizoma encapsulated.

Acute lung injury (ALI), a clinical syndrome of acute respiratory failure due to acute lung inflammation, remains a substantial public health problem in the worldwide. Ligusticum Chuanxiong Rhizoma and Angelicae Sinensis Radix was herb-pair of the traditional Chinese medicine. Modern pharmacological studies have shown that volatile oil extracted from Chuanxiong Rhizome and Angelicae Sinensis Radix is identified as an important active ingredient, which has good antipyretic, analgesic and anti-inflammatory effects. However, whether their volatile oil combination (CA-VO), has effects on the prevention and treatment of ALI has not been reported yet. Due to poor water solubility and low oral bioavailability of CA-VO, CA -VO-loaded microemulsion (CA-VO-ME) was formulated to enhance its oral bioavailability. The physical properties of CA-VO-ME were characterized. The pharmacokinetic parameters and the effect on ALI were evaluated. The particle size, polydispersity index, zeta potential, and encapsulation efficiency of CA-VO-ME were 20.19 ± 0.08 nm, 0.091 ± 0.01, 36.33 ± 4.29%, and 93.75%, respectively. CA-VO-ME had a greater bioavailability (214%) than CA-VO. CA-VO-ME reduced the lipopolysaccharide (LPS)-induced increase in levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in vitro and/or in vivo. Moreover, CA-VO-ME treatment notably decreased the lung index, ameliorated histopathological changes and prolonged the survival of ALI mice. By comparison, CA-VO-ME exerted a better effect on ALI than CA-VO, suggesting that CA-VO-ME is a promising drug for the treatment of ALI.

Epigallocatechin-3-gallate reduces liver and immune system damage in Acinetobacter baumannii-loaded mice with restraint stress.

AIM: Due to the significant increase in the antimicrobial resistance of Acinetobacter baumannii (A. baumannii), new drugs to block the progression of infection are strongly needed. Epigallocatechin-3-gallate (EGCG), a major component of green tea, has exhibited potential activity against A. baumannii in vitro. The aim of this study was to determine if EGCG could be used for pretreating stress-related effects, liver damage, and immune dysfunction caused by A. baumannii infection in vivo. METHODS: Levels of stress hormones, oxidative stress, liver damage, and immune components were analyzed in a murine infection model in which the mice were pretreated with EGCG for one week then intranasally inoculated with A. baumannii. The mice were restrained for 12 h to promote infection because A. baumannii is an opportunistic pathogen. The pretreatment efficacy of EGCG against A. baumannii in mice was assessed for 24 h after the bacterial infection. RESULTS: Restraint stress strengthened the damage from the A. baumannii infection. Pretreatment with EGCG in the murine pneumonia model markedly reduced stress hormones, oxidative metabolites, and proinflammatory cytokine production. EGCG also increased the immune function by increasing the levels of sIgA, T cells and neutrophils after infection. Moreover, pretreatment with EGCG significantly decreased the liver damage by inhibiting the levels of transaminases, oxidative stress metabolites, and cytokines, while maintaining the normal activity of CYP450 enzymes in the liver. CONCLUSION: EGCG was efficacious as a preventative treatment for the damage seen in an experimental model of A. baumannii infection.