S-amlodipine induces liver inflammation and dysfunction through the alteration of intestinal microbiome in a rat model.

S-amlodipine, a commonly prescribed antihypertensive agent, is widely used in clinical settings to treat hypertension. However, the potential adverse effects of long-term S-amlodipine treatment on the liver remain uncertain, given the cautionary recommendations from clinicians regarding its administration in individuals with impaired liver function. To address this, we conducted a study using an eight-week-old male rat model and administered a daily dose of 0.6 ~ 5 mg/kg of S-amlodipine for 7 weeks. Our findings demonstrated that 1.2 ~ 5 mg/kg of S-amlodipine treatment induced liver inflammation and associated dysfunction in rats, further in vitro experiments revealed that the observed liver inflammation and dysfunction were not attributable to direct effects of S-amlodipine on the liver. Metagenome sequencing analysis revealed that S-amlodipine treatment led to alterations in the gut microbiome of rats, with the bloom of E. coli (4.5 ~ 6.6-fold increase) and a decrease in A. muciniphila (1,613.4 ~ 2,000-fold decrease) and B. uniformis (20.6 ~ 202.7-fold decrease), subsequently causing an increase in the gut bacterial lipopolysaccharide (LPS) content (1.4 ~ 1.5-fold increase in feces). S-amlodipine treatment also induced damage to the intestinal barrier and increased intestinal permeability, as confirmed by elevated levels of fecal albumin; furthermore, the flux of gut bacterial LPS into the bloodstream through the portal vein resulted in an increase in serum LPS content (3.3 ~ 4-fold increase). LPS induces liver inflammation and subsequent dysfunction in rats by activating the TLR4 pathway. This study is the first to show that S-amlodipine induces liver inflammation and dysfunction by perturbing the rat gut microbiome. These results indicate the adverse effects of S-amlodipine on the liver and provide a rich understanding of the safety of long-term S-amlodipine administration.

Porphyromonas gingivalis exacerbates alcoholic liver disease by altering gut microbiota composition and host immune response in mice.

AIM: Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, increases the risk of systemic diseases. P. gingivalis infection is closely associated with alcoholic liver disease (ALD), but the underlying mechanism remains unclear. We aimed to investigate the role of P. gingivalis in the pathogenesis of ALD. MATERIALS AND METHODS: An ALD mouse model was established using a Lieber-DeCarli liquid diet, and C57BL/6 mice were treated with P. gingivalis to detect the pathological indicators of ALD. RESULTS: Oral administration of P. gingivalis exacerbated alcohol-induced alterations in the gut microbiota, leading to gut barrier dysfunction and inflammatory response and disruption of the T-helper 17 cell/T-regulatory cell ratio in the colon of ALD mice. Furthermore, P. gingivalis worsened liver inflammation in ALD mice by increasing the protein expression of toll-like receptor 4 (TLR4) and p65, increasing the mRNA expression of interleukins-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) and up-regulating the transforming growth factor-beta 1 (TGF-ß1) and galectin-3 (Gal-3) production. CONCLUSIONS: These results indicate that P. gingivalis accelerates the pathogenesis of ALD via the oral-gut-liver axis, necessitating a new treatment strategy for patients with ALD complicated by periodontitis.

Algicidal properties of extracts from Cinnamomum camphora fresh leaves and their main compounds.

Plant allelochemicals are considered as the source of effective, economic and friendly-environmental algaecides. To uncover the anti-algal activities of Cinnamomum camphora fresh leaves and their main algicidal agents, we investigated the inhibitory effects of water and methanol extracts from C. camphora fresh leaves on Microcystis aeruginosa and Chlamydomonas reinhardtii cell growth, analyzed the composition of the water and methanol extracts, and determined the main compounds in extracts on the growth of the two algae and their anti-algal mechanism from photosynthetic abilities. Water and methanol extracts from C. camphora fresh leaves can inhibit M. aeruginosa and C. reinhardtii cell growth, and methanol extracts showed stronger inhibitory effects, due to their more compounds and higher molar concentration. There were 23 compounds in the water extracts, mainly including terpenoids, esters, alcohols, and ketones. Compared to the water extracts, 9 new compounds were detected in the methanol extracts, and the molar concentration of total compounds in methanol extracts increased by 1.3 folds. Camphor, α-terpineol and linalool were 3 main compounds in the water and methanol extracts. Their mixture (1: 3: 6) and individual compound showed remarkable inhibition on M. aeruginosa and C. reinhardtii cell growth. The degradation of photosynthetic pigments and the reduction of maximum quantum yield of photosystem II (PSII) photochemistry, coefficient of photochemical quenching as well as apparent electron transport rate in C. reinhardtii cells aggravated gradually with increasing the concentration of the mixture and individual compound, while the non-photochemical dissipation of absorbed light energy increased gradually, which led to the decline of photosynthetic abilities. This indicated that camphor, α-terpineol and linalool were 3 main algicidal agents in C. camphora fresh leaf extracts, and they inhibited algal growth by inducing photosynthetic pigment degradation and declining PSII efficiency. Therefore, C. camphora fresh leaf extracts and their main components have potential utilization values as algaecides.

Effects of nitrogen nutrients on the volatile organic compound emissions from Microcystis aeruginosa.

Cyanobacteria release abundant volatile organic compounds (VOCs), which can poison other algae and cause water odor. To uncover the effects of nitrogen (N) nutrients on the formation of cyanobacteria VOCs, the cell growth, VOC emission and the expression of genes involving in VOC formation in Microcystis aeruginosa were investigated under different N conditions. With the supplement of NaNO3, NaNO2, NH4Cl, urea, Serine (Ser) and Arginine (Arg) as the sole N source, NaNO3, urea and Arg showed the best effects on M. aeruginosa cell growth, and limited N supply inhibited the cell growth. M. aeruginosa released 26, 25, 23, 27, 23 and 25 compounds, respectively, in response to different N forms, including furans, sulfocompounds, terpenoids, benzenes, hydrocarbons, aldehydes, and esters. Low-N especially Non-N condition markedly promoted the VOC emission. Under Non-N condition, four up-regulated genes involving in VOC precursor formation were identified, including the genes of pyruvate kinase, malic enzyme and phosphotransacetylase for terpenoids, the gene of aspartate aminotransferase for benzenes and sulfocompounds. In eutrophic water, cyanobacteria release different VOC blends using various N forms, and the reduction of N amount caused by cyanobacteria massive growth can promote algal VOC emission by up-regulating the gene expression.

Inhibitory effects of extracts from Cinnamomum camphora fallen leaves on algae.

Natural allelochemicals are considered as a source of algaecides. To uncover the anti-algal activity of Cinnamomum camphora fallen leaves and promote their usage as algaecides, the composition of their water and methanol extracts was analyzed, and the inhibitory effects of extracts on the growth of Microcystis aeruginosa and Chlamydomonas reinhardtii, and chlorophyll (Chl) content and photosynthetic abilities in C. reinhardtii were investigated. Twenty-five compounds were detected in the water extracts, mainly including terpenoids, esters, alcohols, and ketones. Compared to water extracts, there were more compounds and higher concentration in methanol extracts. Both water and methanol extracts inhibited the growth of the two algae, and 15 mg·ml-1 methanol extracts killed the algal cells after 48 h. The levels of Chl a and Chl b, as well as maximum quantum yield of photosystem II photochemistry (Fv/Fm) in C. reinhardtii cells reduced gradually with increasing the concentration of extracts, while the maximum quantum yield of non-photochemical de-excitation (φDO) increased gradually. At the same concentration, methanol extracts showed stronger inhibitory effects than water extracts, due to their higher number of compounds and higher concentration. Therefore, C. camphora fallen leaves have a potential value as an algaecide.