Background: Traditional Chinese medicine (TCM) formulations have proven to be advantageous in clinical treatment and prevention of disease. LiuWei DiHuang Pill (LWDH Pill) is a TCM that was employed to treat type 2 diabetes mellitus (T2DM). However, a holistic network pharmacology approach to understanding the active ingredients and the therapeutic mechanisms underlying T2DM has not been pursued. Methods: A network pharmacology approach including drug-likeness evaluation, oral bioavailability prediction, virtual docking, and network analysis has been used to predict the active ingredients and potential targets of LWDH Pill in the treatment of type 2 diabetes. Results: The comprehensive network pharmacology approach was successfully to identify 45 active ingredients in LWDH Pill. 45 active ingredients hit by 163 potential targets related to T2DM. Ten of the more highly predictive components (such as :quercetin, Kaempferol, Stigmasterol, beta-sitosterol, Kadsurenone, Diosgenin, hancinone C, Hederagenin, Garcinone B, Isofucosterol) are involved in anti-inflammatory, anti-oxidative stress, and the reduction of beta cell damage. LWDH Pill may play a role in the treatment of T2DM and its complications (atherosclerosis and nephropathy) through the AGE-RAGE signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. Conclusion: Based on a systematic network pharmacology approach, our works successfully predict the active ingredients and potential targets of LWDH Pill for application to T2DM and helps to illustrate mechanism of action on a comprehensive level. This study provides identify key genes and pathway associated with the prognosis and pathogenesis of T2DM from new insights, which also demonstrates a feasible method for the research of chemical basis and pharmacology in LWDH Pill.

The sweet rhizomes of Polygonatum cyrtonema are widely used as a tonic and functional food. A sensitive and rapid analytical method was developed for simultaneous identification and dynamic analysis of saccharides during steam processing in P. cyrtonema using HPLC–QTOF–MS/MS. Fructose, sorbitol, glucose, galactose, sucrose, and 1-kestose were identified, as well as a large number of oligosaccharides constituted of fructose units through β-(2→1) or β-(2→6). Polysaccharides and oligosaccharides were decomposed to monosaccharides during a steaming process, since the contents of glucose, galactose, and fructose were increased, while those of sucrose, 1-kestose, and polysaccharides were decreased. The high content of fructose was revealed to be the main determinant for increasing the level of sweetness after steaming. The samples of different repeated steaming times were shown to be well grouped and gradually shift along the PC1 (72.4%) axis by principal component analysis. The small-molecule saccharides, especially fructose, could be considered as markers for the steaming process of rhizomes of P. cyrtonema.

Introduction:Polygonatum cyrtonema Hua (PC) is an essential herbal medicine in China, known for improving muscle quality and enhancing physical function; its active ingredients are polysaccharides (PCPs). A previous study revealed the anti-atrophy effects of PCPs in cachectic mice. However, whether the effects of PCPs on anti-atrophy are associated with gut microenvironment remain elusive. This research endeavored to assess the medicinal efficacy of PCPs in alleviating muscle atrophy and fat lipolysis and explore the potential mechanisms.Methods: A cancer cachexia model was induced by male C57BL/6 mice bearing Lewis lung tumor cells and chemotherapy. The pharmacodynamics of PCPs (32 and 64 mg/kg/day) was investigated through measurements of tumor-free body weight, gastrocnemius muscle weight, soleus muscle weight, epididymal fat weight, tissue histology analysis, and pro-inflammatory cytokines. Immunohistochemistry and Western blotting assays were further used to confirm the effects of PCPs. 16S rRNA sequencing, LC-MS and GC-MS-based metabolomics were used to analyze the gut microbiota composition and metabolite alterations. Additionally, the agonist of free fatty acid receptor 2 (FFAR2)—a crucial short-chain fatty acid (SCFA) signaling molecule—was used to investigate the role of gut microbiota metabolites, specifically SCFAs, in the treatment of cancer cachexia, with comparisons to PCPs.Results: This study demonstrated that PCPs significantly mitigated body weight loss, restored muscle fiber atrophy and mitochondrial disorder, alleviated adipose tissue wasting, strengthened the intestinal barrier integrity, and decreased the intestinal inflammation in chemotherapy-induced cachexia. Furthermore, the reversal of specific bacterial taxa including Klebsiella, Akkermansia, norank_f__Desulfovibrionaceae, Enterococcus, NK4A214_group, Eubacterium_fissicatena_group, Eubacterium_nodatum_group, Erysipelatoclostridium, Lactobacillus, Monoglobus, Ruminococcus, Odoribacter, and Enterorhabdus, along with alterations in metabolites such as amino acids (AAs), eicosanoids, lactic acid and (SCFAs), contributed to the therapeutic effects of PCPs.Conclusion: Our findings suggest that PCPs can be used as prebiotic drugs targeting the microbiome–metabolomics axis in cancer patients undergoing chemotherapy.