Epidemiological studies have reported varying associations between coffee consumption and bone mineral density. This study aims to systematically asses the pharmacological effects of prolonged coffee intake on osteoblasts, osteoclasts, and postmenopausal osteoporosis induced by ovariectomy. In vitro, experiments revealed that coffee water extract upregulated the expression of osteogenic-related proteins such as 12.5 μg/mL middle concentration group had a 1.33 fold increase in collagen type Ⅰ α 1 (COL1A1) expression, and a 1.83 fold increase in Osterix expression by inhibiting the phosphorylation of protein kinase B (AKT), inhibitor of κB protein-α (IκBɑ), P65, and extracellular signal-regulated kinase (ERK). Additionally, it inhibited receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclastogenesis in RAW264.7 cells though the AKT, MAPKs, and NF-κB pathways, concomitant with the inhibition of nuclear translocation of nuclear factor of activated T cells cytoplasmic 1. In vivo studies demonstrated that a medium-dose coffee sample inhibited osteoclastogenesis, stimulated osteogenesis, and ameliorated bone loss in ovariectomized mice. Molecular docking analysis validated the impact of caffeine, cholorogenic acids, and trigonelline on bone homeostasis. In summary, consumption of 4?5 cups of coffee per day in humans may attenuate ovariectomy (OVX)-associated pathological bone loss by disrupting osteoclast activity and promoting osteogenesis, while long-term consumption of high-dose coffee could disrupt bone homeostasis.

The objective of the study is to investigate the effect of ripe Pu-erh tea on the antioxidant enzyme activity, the morphology of small intestine, and the diversity and structural change of intestinal flora in D-galactose-induced aging mice. In this study, C57/BL6 mice were randomly divided into a control group, an aging group and a ripe Pu-erh tea group. A mouse model of aging was created by subcutaneous injection of D-galactose. After 18 weeks of oral administration, the changes in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), malondialdehyde (MDA) content, and small intestinal histopathology were evaluated and the intestinal flora structure was analyzed by 16S rDNA high-throughput sequencing. The results showed that SOD and GSH-Px activities were significantly decreased and MDA content was significantly increased in D-gal induced aging mice (P < 0.05). Compared to the aging and group, SOD and GSH-Px activities were significantly increased and MDA content was significantly decreased in the ripe Pu-erh tea group (P < 0.05). In the hematoxylin-eosin (HE) staining test, compared to the control group, the intestinal villus length, crypt depth and muscle layer thickness of mice were significantly decreased in the aging group (P < 0.05). After the intervention with ripe Pu-erh tea, the intestinal flora structure was improved compared to the aging mice (P < 0.05); the ratio of Bacteroidetes to Firmicutes was significantly increased (P < 0.05), the relative abundance of Lactobacillaceae and Lactobacillus was significantly decreased (P < 0.05), and the relative abundance of Ruminococcaceae was significantly increased (P < 0.05). In summary, we conclude that Pu-erh ripe tea can improve intestinal environmental disorders in D-gal induced aging mice at doses three times higher than the normal level, thereby delaying the aging process.

Delaying aging has become a hot spot of social concern and research. Our previous studies have shown that ripe Pu-erh tea can delay aging in mice by regulating the intestinal flora, but the metabolites in response to endogenous substances in mice are not clear. In this paper, the Morris water maze test was used to detect learning and memory capacity in control, D-galactose-induced aging, and ripe Pu-erh tea-treated mice. Non-targeted metabolomics was used to detect metabolites in the brain tissue and serum of mice from each group for the purpose of exploring the anti-aging effect of ripe Pu-erh tea on D-galactose-induced aging mice, screening differential metabolites among the three groups and analyzing the related metabolic pathways. The results showed that ripe Pu-erh tea improved learning capacity, and regulated 26 differential metabolites in the brain tissue of aging mice, mainly involved in the glycerophospholipid metabolism, vitamin B₆ metabolism, histidine metabolism and purine metabolism pathways, among which the glycerophospholipid metabolism and histidine metabolism pathway were the most significant. A total of 11 differential metabolites were identified in serum, mainly involved in the metabolism of vitamin B₆ and arachidonic acid, among which vitamin B₆ metab olism pathway was the most significant. After the intervention with ripe Pu-erh tea, the contents of glycerophospholipid metabolites including phosphatidylcholine [PC (20:5/20:4)], phosphatidyl ethanlamine [PE (22:2/14:0)], phosphatidylserine [PS (20:5/18:1)] and lysophosphatidylcholine [LysoPC (18:2)], the histidine metabolite carnosine, and the vitamin B₆ metabolite pyridoxal 5’-phosphate were significantly increased in aging mice. These results suggest that ripe Pu-erh tea can delay aging by regulating lipid and amino acid metabolism.