Effects of climate warming and human activities on the distribution patterns of Fritillaria unibracteata in eastern Qinghai-Tibetan Plateau.

Fritillaria unibracteata is an endangered medicinal material species endemic to the Qinghai Tibet Plateau, and belongs to the national Class III endangered plant. In addition to expelling wind and removing damne, it also warms menstruation and relieves pain in clinic use of tranditional Chinese medicine. In recent years, affected by the destruction of shrubs and climate change, the habitat of F. unibracteata wild resources has been seriously damaged, indicating of great significance to predict its potential suitable habitat using MaxEnt model. The AUC values without human activities were 0.983 ± 0.013-0.988 ± 0.001, while it is 0.982 ± 0.015-0.989 ± 0.000 with human activities, justifying their applications for predicting the potential areas of F. unibracteata. Without human activities, there were 8.47 × 104 km2 of highly suitable habitats in northern Sichuan, southern Gansu and southeastern Qinghai. But the poorly, moderately and highly suitable areas of F. unibracteata have decreased to 33.8 × 104 km2, 9.66 × 104 km2 and 6.64 × 104 km2 due to human activities. Environmental variables affecting F. unibracteata distribution included the minimum temperature in the coldest month (-16.89--4.96 °C), annual precipitation (416.64-866.96 mm), temperature annual range (24.83-31.97 °C), elevation (2879.69-3981.82 m), human footprint (2.58-23.66) and mean UV-B of highest month (7381.92-8574.27 kJ/m2). In the 2050s and 2090s, human activities would significantly reduce the highly suitable habitats of F. unibracteata. Under SSP1-2.6, SSP2-4.5 and SSP5-8.5 scenarios, the centroid would move to the low latitude area from the current position first, and then to a high latitude area. Wild resources of F. unibracteata in China can be effectively conserved based on our results.

Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-[Formula: see text]B/HIF-1α Pathway in CCl4-Induced Liver Fibrosis.

Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl4. In addition, the RAW264.7 macrophages were cultured in the presence of CoCl2 to simulate a hypoxic microenvironment of fibrotic livers in vitro. The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the in vivo and in vitro models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl4-induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both in vivo and in vitro. Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.