Background: Tauroursodeoxycholic acid (TUDCA) treatment significantly decreases the blood sugar content and exerts renoprotective effects in db/db mice. These changes are likely related to endoplasmic reticulum (ER) stress and apoptosis inhibition.

Purpose: To elucidate the mechanism underlying the association between the renoprotective effect of TUDCA and ER stress inhibition.

Methods: Renal proximal tubular cells (HK-2 (Human Kidney-2) cells) were cultured with or without TUDCA (0.1, 0.2, and 0.4 mmol/L) in normal or high-concentration glucose (HG) media. After 48 h, we determined the HK-2 apoptosis and proliferation rates by flow cytometry and methyl thiazol tetrazolium (MTT) assay, respectively. Furthermore, we detected intracellular reactive oxygen species (ROS) levels and the mitochondrial membrane potential per group. Finally, we analyzed the expression of ER stress-related markers using western blotting and real-time polymerase chain reaction.

Results: TUDCA treatment protected HK-2 cells from HG damage, reduced apoptosis, and restored cell proliferation inhibited by HG through the ER stress pathway. The protective effect on HK-2 cells corresponded with ROS inhibition and mitochondrial membrane potential stabilization. Additionally, TUDCA treatment downregulated CCAAT enhancer binding protein (C/EBP) homologous protein (i.e., CHOP) and glucose-regulated protein: 78 kDa (i.e., GRP78) expression, which were upregulated in the HG group.

Conclusions: Our results suggest that TUDCA protected renal proximal tubular cells against HG-induced apoptosis by suppressing ER stress.

Background: One of the most popular drinks in the world is caffeine, which is known to produce anxiety symptoms that are clinical in nature. There are numerous classes of anxiolytics in the market. Still, there is always a need to find safe substitutes for medications because of their poor effectiveness and long-term side effects. This study aimed to investigate the anxiolytic effects of Manilkara zapota (MZ) leaf extract on caffeine-induced anxiety in mice.

Methods: The study was conducted on albino mice, in which anxiety disease was induced with a caffeine dose of 25 mg/kg by intraperitoneal (i.p) route. The animals were pretreated with different drugs for 14 days and caffeine was administered during the last 7 days of the treatment. The mice were randomly divided into 6 groups with 6 animals each, including control, caffeine (used for inducing anxiety), diazepam (1 mg/kg by oral route, as reference standard), and three doses of MZ (150, 300, and 450 mg/kg orally). Various behavioral, biochemical, and histopathological parameters were evaluated in caffeine-induced anxiety.

Results: MZ leaf extract demonstrated a significant increase in behavioral activity. In light/dark exploration (LDE), the extract significantly increased (p < 0.01) the duration spent in the light chamber and the number of switches from light to dark, which was otherwise diminished by caffeine. Similarly, in the open field test (OFT), the extract shows a significant increase (p < 0.001) in the number of rearing and the squares crossed. In the force swim test (FST), the extract showed an increase in the immobility time compared to the inducer. Compared to the caffeine-treated group, there was a significant increase (p < 0.01) in the levels of catalase, glutathione, and serotonin in the extract-treated groups. The histopathological changes showed a considerable decrease in the caffeine-induced damage in the brain and showed normal morphology in the hippocampus (dentate gyrus) region.

Conclusion: In the present study, data suggested that MZ extract exhibited anxiolytic-like activity. The observed activity could be linked to enhanced antioxidant status that was responsible for restoring the serotonin level and preventing structural damage in the brain. More research might provide a cost-effective alternative source for treating anxiety disorders.

Objective: Microbiota change has been recognized as an important player in the progression of inflammatory bowel diseases (IBDs). This study aims to evaluate the beneficial effect of rauvolfian pectic polysaccharide (PP) on mucosal inflammation and its impact on gut microbiota.

Methods: Rauvolfian PP from Rauvolfia callus was prepared as intervention photochemical. Gut inflammation was induced by dextran sulfate sodium (DSS) in the mouse model and the beneficial effect of PP administration on colitis was evaluated. The microbiota composition in control group, DSS model group and DSS with PP treatment group was examined by integrative sequencing of 16S, 18S and internal transcribed spacer (ITS) targets using genomic DNA from the fecal samples.

Results: We reported the beneficial effect of rauvolfian PP in alleviating the colitis and suppressing pyroptosis in intestinal mucosa of DSS-induced mouse model. Both colitis induction and PP administration significantly altered the composition of intestinal microbiota. DSS induced colitis decreased gut microbial diversity, and PP treatment further lower the diversity of gut microbiota. Interestingly, the abundance of Escherichia-Shigella and Citrobacter became increased after PP administration.

Conclusions: Our data revealed the microbiota changes associated with the beneficial effect of rauvolfian PP in colitis model. The overall reduction of microbiota diversity and the increased abundance of specific microbial families may account for the beneficial effect of PP administration. Future work needs to focus on the elucidation of the mechanisms by which these microbial families may help alleviate the progression of IBD.

Background: Mondia whitei, an indigenous African plant, is widely recognised for its medicinal properties. Throughout ancient times, African communities have employed this remedy to address a wide range of health conditions. However, there is a lack of online High-Performance Liquid Chromatography (HPLC) studies available for this plant. The present investigation aimed to address and alleviate this deficiency by providing a comprehensive analysis.

Methods: Methanol, combination of water and methanol, ethyl acetate, and water extracts of Mondia whitei (M. whitei) leaves were utilized in this study. The phenolic and flavonoids composition of the extracts determined by Folin-Ciocalteu and Aluminum chloride (AlCl₃) assays, respectively. The antioxidant potential of all the extracts was assessed through a range of in vitro assays, including FRAP (Ferric reducing antioxidant power), DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS [2,2′-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)], CUPRAC (cupric reducing antioxidant capacity), PBD (phosphomolybdenum), and MCA (metal chelating ability). Subsequently, the online HPLC-linked system had established to compare these extracts using four distinct antioxidant analysis methods: FRAP, DPPH, ABTS, and CUPRAC. The enzyme inhibitory properties were also investigated against cholinesterases, tyrosinase, α-amylase and α-glucosidase.

Results: The methanol-water and methanol extracts had the highest phenolic contents and demonstrated superior efficacy as scavenging/reducing agents and enzyme inhibitors, particularly against tyrosinase and cholinesterase (p < 0.05). Through the utilisation of various online HPLC antioxidant techniques, the identification of four molecules exhibiting antioxidant activity was achieved. These compounds were identified as Coumarin, Vanillin, p-OH benzoic acid, and Chlorogenic acid.

Conclusions: Mondia whitei leaves can be regarded as a valuable source of natural bioactive compounds, with the potential to serve as a material basis for pharmacological effects in nutraceutical and pharmaceutical applications.

Background: Drug-induced acute liver damage is a contributing factor in nearly 50% of acute liver failures. Acute liver failure has been linked to pharmaceutical overdoses, particularly with paracetamol. Plant-based medication could be a possible agent for mitigating the effects of paracetamol overdose. The present study investigated Pimenta dioica (PD) berries extract for its hepatoprotective properties against paracetamol-induced liver toxicity in rats.

Materials and Methods: Two chemicals, paracetamol and silymarin, were used in this study. Furthermore, fully mature berries of PD were used to extract the bioactive constituents in 90% ethanol. Moreover, male Wistar albino rats (n = 40) were used to assess the hepatoprotective activity. For this purpose, hepatotoxicity was induced by orally administering 2 g/kg body weight of paracetamol. The rats were divided into five groups. Group I (control group) received 1 mL/kg of 1% sodium carboxymethyl cellulose. Group II (hepatotoxic control group) received an oral dose of 2 g/kg of paracetamol. Group III was given silymarin at a dose of 100 mg/kg. Group IV and V received PD at 200 mg/kg and 400 mg/kg, respectively. The liver was surgically excised to calculate relative liver weight and histopathological examination in different rat groups. Blood samples were collected from the retro-orbital plexus on the 8th day of treatment and examined for serum alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TB) content, and gamma-glutamyl transferase (GGT) levels. The data were statistically analyzed using a one-way Analysis of Variance (ANOVA), with a p-value < 0.05 considered significant.

Results: It was observed that paracetamol significantly increased (p < 0.001) relative liver weight as well as liver biomarker enzymes such as ALP, ALT, AST, TB, and GGT. Furthermore, paracetamol caused histological alterations in the hepatocytes. Moreover, Pimenta dioica (PD) significantly inhibited (p < 0.001) paracetamol-induced changes in relative liver weight, liver biomarkers levels, and hepatocyte histopathology in a dose-dependent manner.

Conclusion: These findings suggest that PD possesses hepatoprotective properties against paracetamol-induced hepatocellular damage. Although, based on the current findings, it is difficult to speculate on the precise mechanism of action, attenuation of paracetamol-induced generation of free radicals could be one of the mechanisms. Therefore, further investigation to identify potentially active components and to establish the precise mechanism of action for its hepatoprotective effect could make PD a novel candidate for therapeutic use.

Background: Liuwei Dihuang pills contain quercetin, which has been found to alleviate postmenopausal osteoporosis (PMOP) progression. This study aimed to investigate the effects of quercetin on the intestinal microbiota and microbial metabolism in rats suffering from PMOP.

Methods: The Sprague Dawley female rats were randomly divided into four groups (n = 5): sham, ovariectomized (OVX), quercetin-low dose (50 mg/kg/d), and quercetin-high dose (100 mg/kg/d). The optimal dose group (quercetin-high dose group) was used as the quercetin group for follow-up experiments. The histopathological changes in the tibia of rats were observed using hematoxylin-eosin (HE) and Masson staining. The composition and abundance of intestinal microbiota were determined using 16S rRNA sequencing, while metabolite levels were assessed using metabolomics. Pearson's correlation analysis was used to investigate the relationship between microbiota abundance and metabolite levels.

Results: The administration of quercetin helped to prevent the degradation of the collagen fiber layer on the surface and the formation of fibrosis of femur tissue caused by OVX. Additionally, treatment with quercetin significantly increased species abundance and evenness in the OVX group. In contrast to the OVX group, quercetin treatment increased Muribaculaceae abundance and decreased the Clostridium sensu stricto 1 abundance. Major differential metabolites, such as pregnenolone, 3-aminobutyric acid, 2-aminoisobutyrate, N-methyl-L-alanine, and aminoisobutanoate, were found between the OVX and quercetin groups. Correlations between the abundance of Muribaculaceae and Clostridia UCG 014 and the major differential metabolites were found, respectively. Furthermore, the amino acid metabolic pathways were found to be the primary pathway for intestinal microbiota.

Conclusions: The active ingredient quercetin regulates intestinal microbiota and microbial metabolism, helping to alleviate the symptoms of PMOP in rats.

Background: Focal segmental glomerulosclerosis is the leading cause of kidney disease worldwide. The potential effect of quercetin on glomerulosclerosis was identified using quantification-based proteomic analysis.

Methods: Glomerulosclerosis was induced using adriamycin in rats treated with quercetin for 8 weeks starting on the day of adriamycin injection. Next, significant differentially expressed proteins (DEPs) were identified through label-free quantification-based proteomic analysis of renal samples. Functional analysis was performed to evaluate the effects of quercetin on glomerulosclerosis.

Results: In this study, 26,431 peptides and 5272 proteins were identified using quantification-based proteomic analysis. Clusters of Orthologous Groups analysis identified general function prediction as the only key initiation factor in the glomerulosclerosis process. Gene Ontology analysis showed that these DEPs were parsed into six major components: cell, cell part, cellular process, binding organelle, single-organism process, and metabolic process. Kyoto Encyclopedia of Genes and Genomes analysis revealed 803 DEPs involved in metabolic pathways. Notably, DEPs were distributed in the PI3K-Akt signaling pathway at a proportion of 3.08%. We showed that quercetin substantially contributes to the protection against glomerulosclerosis through the extracellular region. Quercetin can also inhibit the progression of glomerulosclerosis through the PI3K/Akt pathway.

Conclusions: These results suggest a novel therapeutic approach for glomerulosclerosis.