Fuzi Lizhong Pills alter microbial community compositions and metabolite profiles in ulcerative colitis rat with Spleen-Kidney Yang Deficiency Syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel condition that is frequently related with Spleen-Kidney Yang Deficiency Syndrome (SKYD) in Chinese medicine. Fuzi Lizhong Pill (FLZP), a traditional medicine for SKYD, has been utilized in China for generations, although the exact mechanism by which it treats UC is unknown. AIM OF THE STUDY: The goal of this study is to further understand FLZP's therapeutic mechanism in SKYD-associated UC. MATERIALS AND METHODS: To investigate the impact of FLZP on SKYD-associated UC, we used a comprehensive method that included serum metabolomics and gut microbiota profiling. The chemical composition of FLZP was determined using mass spectrometry. UC rats with SKYD were induced and treated with FLZP. Serum metabolomics and 16S rRNA microbial community analysis were used to evaluate FLZP's effects on endogenous metabolites and gut microbiota, respectively. Correlation analysis investigated the association between metabolites and intestinal flora. A metabolic pathway analysis was undertaken to discover putative FLZP action mechanisms. RESULTS: FLZP contains 109 components, including liquiritin (584.8176 µg/g), benzoylaconine (16.3087 µg/g), benzoylhypaconine (31.9583), and hypaconitine (8.1160 µg/g). FLZP predominantly regulated seven metabolites and eight metabolic pathways involved in amino acid and nucleotide metabolism, with an emphasis on energy metabolism and gastrointestinal digestion. FLZP also influenced intestinal flora variety, increasing probiotic abundance while decreasing pathogenic bacteria prevalence. An integrated investigation identified associations between changes in certain gut flora and energy metabolism, specifically the tricarboxylic acid (TCA) cycle. CONCLUSIONS: FLZP successfully cures UC in SKYD rats by regulating amino acid and energy metabolism. Its positive effects may include altering microbiota composition and metabolite profiles in UC rats with SKYD. These findings shed light on FLZP's mode of action and its implications for UC management.

Unlocking the hidden potential: Enhancing the utilization of stems and leaves through metabolite analysis and toxicity assessment of various parts of Aconitum carmichaelii.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii is widely used in traditional Chinese medicine clinics as a bulk medicinal material. It has been used in China for more than two thousand years. Nevertheless, the stems and leaves of this plant are usually discarded as non-medicinal parts, even though they have a large biomass and exhibit therapeutic properties. Thus, it is crucial to investigate metabolites of different parts of Aconitum carmichaelii and explore the relationship between metabolites and toxicity to unleash the utilization potential of the stems and leaves. AIM OF THE STUDY: Using plant metabolomics, we aim to correlate different metabolites in various parts of Aconitum carmichaelii with toxicity, thereby screening for toxicity markers. This endeavor seeks to offer valuable insights for the development of Aconitum carmichaelii stem and leaf-based applications. MATERIALS AND METHODS: UHPLC-Q-Orbitrap MS/MS-based plant metabolomics was employed to analyze metabolites of the different parts of Aconitum carmichaelii. The cardiotoxicity and hepatotoxicity of the extracts from different parts of Aconitum carmichaelii were also investigated using zebrafish as animal model. Toxicity markers were subsequently identified by correlating toxicity with metabolites. RESULTS: A total of 113 alkaloids were identified from the extracts of various parts of Aconitum carmichaelii, with 64 different metabolites in stems and leaves compared to daughter root (Fuzi), and 21 different metabolites in stems and leaves compared to mother root (Wutou). The content of aporphine alkaloids in the stems and leaves of Aconitum carmichaelii is higher than that in the medicinal parts, while the content of the diester-diterpenoid alkaloids is lower. Additionally, the medicinal parts of Aconitum carmichaelii exhibited cardiotoxicity and hepatotoxicity, while the stems and leaves have no obvious toxicity. Finally, through correlation analysis and animal experimental verification, mesaconitine, deoxyaconitine, and hypaconitine were used as toxicity markers. CONCLUSION: Given the low toxicity of the stems and leaves and the potential efficacy of aporphine alkaloids, the stems and leaves of Aconitum carmichaelii hold promise as a valuable medicinal resource warranting further development.

Chronic cold environment regulates rheumatoid arthritis through modulation of gut microbiota-derived bile acids.

The pathologies of many diseases are influenced by environmental temperature. As early as the classical Roman age, people believed that exposure to cold weather was bad for rheumatoid arthritis (RA). However, there is no direct evidence supporting this notion, and the molecular mechanisms of the effects of chronic cold exposure on RA remain unknown. Here, in a temperature-conditioned environment, we found that chronic cold exposure aggravates collagen-induced arthritis (CIA) by increasing ankle swelling, bone erosion, and cytokine levels in rats. Furthermore, in chronic cold-exposed CIA rats, gut microbiota dysbiosis was identified, including a decrease in the differential relative abundance of the families Lachnospiraceae and Ruminococcaceae. We also found that an antibiotic cocktail suppressed arthritis severity under cold conditions. Notably, the fecal microbiota transplantation (FMT) results showed that transplantation of cold-adapted microbiota partly recapitulated the microbiota signature in the respective donor rats and phenocopied the cold-induced effects on CIA rats. In addition, cold exposure disturbed bile acid profiles, in particular decreasing gut microbiota-derived taurohyodeoxycholic acid (THDCA) levels. The perturbation of bile acids was also associated with activation of the TGR5-cAMP-PKA axis and NLRP3 inflammasome. Oral THDCA supplementation mitigated the arthritis exacerbation induced by chronic cold exposure. Our findings identify an important role of aberrant gut microbiota-derived bile acids in cold exposure-related RA, highlighting potential opportunities to treat cold-related RA by manipulating the gut microbiota and/or supplementing with THDCA.

Diverse alkaloids from the aerial parts of Aconitum carmichaelii and antiproliferative activity of costemline via inhibiting SIRT1/ROCK1/P-STAT3 pathways.

Six undescribed alkaloids together with 15 known alkaloids were isolated from the aerial parts of Aconitum carmichaelii. Their structures were elucidated extensively by NMR and HRESIMS spectroscopy. The absolute configurations of N-formyllaurotetanine, and the known compounds glaucine-ß-N-oxide and glaucine-α-N-oxide were established by electronic circular dichroism (ECD) spectra. Notably, it was the discovery of rare indole alkaloids from the genus Aconitum, and biosynthetic pathway of compounds 1 and 6 was deduced. Evaluation of the antiproliferative activity of these alkaloids demonstrated that costemline exhibited significant anti-proliferation effects against HCT116, SKOV3, and A549 cells with IC50 values of 5.6, 14.2, and 6.8 µM, respectively. Costemline could also inhibit the cell invasion activity of HCT116 cells. Mechanistic studies in HCT116 cells suggested that the antiproliferative activity of costemline was attributable to SIRT1/ROCK1/P-STAT3 pathways regulation. This study revealed the potential for developing and utilizing the aerial parts of Aconitum carmichaelii.

A comprehensive investigation on the chemical diversity and efficacy of different parts of Ligusticum chuanxiong.

Ligusticum chuanxiong Hort. (CX) is a medicinal and edible plant with a wide range of constituents of biological interest. Since the biomass of the non-medicinal parts of CX is huge, discarding them will cause a waste of resources. To expand the medicinal uses of CX, we comprehensively investigated the chemical diversity and efficacy of its different parts (rhizomes, fibrous roots, stems and leaves). 75 compounds in the volatile oil and 243 compounds in the methanol extracts (including 95 phthalides) obtained from CX were characterized by GC-MS and UHPLC/Q-Orbitrap MS analysis, respectively. Of 95 phthalides, 14 potential new compounds and 5 phthalide trimers were identified from CX for the first time. Phthalide monomers were more abundant in rhizomes and fibrous roots, and phthalide dimers or even phthalide trimers mainly in stems and leaves. By multivariate and univariate analyses, 22 and 24 different compounds were found in the volatile oils and the methanol extracts, respectively. In the bioactivity evaluation of different parts, stems and leaves showed the best antioxidant activity, fibrous roots showed the strongest vasodilator activity, and rhizomes showed the most significant anticoagulant activity, which was related to the different metabolites in different parts. Ultimately, this work revealed the similarities and differences of phytochemicals and bioactivities in different anatomical parts of CX. It might provide helpful evidence for the rational application of non-medicinal resources.