Moringa oleifera have laxative effects, but their active compositions and mechanisms are not very clear thus far. To this end, we systematically explored the active components and mechanism of M. oleifera leaves in relieving constipation by using the slow transit constipation (STC) mouse model and network pharmacology. The results of animal experiments showed that M. oleifera aqueous extract (MOA) had good laxative activity, and its 70% alcohol soluble part (ASP) also showed significant laxative activity (P < 0.01). Network pharmacological prediction results suggested that L-phenylalanine (Phe) was the key compound of ASP, and it might relieve constipation through tachykinin receptor 1 (TACR1) and three kinds of adrenergic receptors, including α_1A (ADRA1A), α_2A (ADRA2A), and α_2B (ADRA2B). Further animal experiment results showed that Phe significantly promoted gastrointestinal motility. Phe may relieve STC by enhancing the release of substance P (SP) and upregulating the mRNA expression of TACR1 in the ileum. Importantly, Phe may also promote intestinal movement by downregulating the mRNA expression of ADRA2A and ADRA2B and upregulating the mRNA expression of Calm and the mRNA and protein expression of myosin light chain 9 in the ileum, thereby activating the G protein-coupled receptor-myosin light chain signaling pathway. These results lay a foundation for the application of M. oleifera and Phe in constipation.

Tumor necrosis factor-α (TNF-α) is a key player in the pathogenesis of rheumatoid arthritis (RA) and considered a promising target for therapeutic drug development. Activation of the nuclear factor-kappa B (NF-κB) pathway upon TNF-α binding to its receptor is crucial for progression of RA. Stephanine (SA), an isoquinoline aporphine-type alkaloid recently identified in Stephania plants, exhibits anti-inflammatory properties, but its underlying mechanisms of action are unknown at present. In this study, we explored whether SA could ameliorate RA through inhibition of the NF-κB signaling pathway in association with TNF-α activity. Our experiments revealed a binding affinity (K_D) of SA for TNF-α of 2.934×10^-6 M. Additionally, SA at a concentration of 10 μmol/L effectively hindered the binding of TNF-α to its receptors TNFR1 and TNFR2. In vitro, SA prevented TNF-α-induced death of L929 cells and blocked NF-κB activation triggered by TNF-α in 293-TNF-α responsive, as well as HFLS and MH7A cell lines. Furthermore, in a collagen-induced arthritis (CIA) mouse model, SA alleviated the symptoms of RA through suppression of NF-κB signaling. Our collective findings support the therapeutic efficacy of SA, a natural compound targeting TNF-α, in the management of RA.

Excessive osteoclastogenesis-mediated osteoporosis has been recognized as a global health concern. Candidate compounds derived from medicinal plants or functional foods are promising to treat osteoporosis due to their high safety and efficiency. (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active polyphenol in green tea. It can inhibit osteoclastogenesis in vitro by blocking RANK signaling pathways. This study used the ovariectomized (OVX) mouse model to estimate the therapeutic effect of EGCG on osteoporosis and verified the molecular mechanism in vivo. The results revealed that EGCG significantly inhibited the OVX-induced body weight gain. Moreover, no adverse effects were observed on blood glucose, histomorphological features, weights, as well as indices of liver and kidney in OVX mice. EGCG could significantly ameliorate bone loss in OVX mice by inhibiting osteoclastogenesis. This effect was evidenced by the reduced number of osteoclasts and the increased trabecular bone area in the femurs. Moreover, EGCG inhibited the activities of CTX-Ⅰ and TRACP-5b and strengthened BGP and PⅠNP activities in OVX mice. Mechanistically, EGCG significantly downregulated the expression of osteoclastogenesis-related marker genes and proteins, including NFATc1, c-Fos, TRAP, c-Src, and cathepsin K. In addition, the phosphorylation levels of p65, JNK, ERK1/2, p38, and AKT were significantly suppressed in OVX mice. It was found that EGCG could alleviate OVX-induced bone loss in mice by suppressing osteoclastogenesis by blocking the NF-κB, MAPK, and AKT signaling pathways. EGCG has the potential to prevent and treat osteoclast-related diseases such as osteoporosis.

Epidemiological studies have demonstrated that a range of metabolic diseases, particularly type 2 diabetes and obesity, have reached epidemic proportions. These chronic conditions not only diminish the equality of life for individuals but also impose significant financial burdens on families and healthcare systems. While various therapeutic medications can effectively manage the progression of these diseases, they often come with adverse side effects. In contrast, natural products and their metabolites, such as ellagic acid (EA) and urolithins derived from a variety of plant species, have gained attention for their wide-ranging biological activities, diverse classes, and minimal side effects. Emerging research suggests that EA and urolithins may offer promising therapeutic effects in the treatment of metabolic disorders. This review aims to provide a comprehensive overview of the therapeutic effects and associated signaling pathways of EA and its metabolite urolithins in various metabolic diseases, offering valuable insights for their clinical applications and the potential development of novel food and medicine homologous therapies.