Therapeutic Mechanism and Key Alkaloids of Uncaria rhynchophylla in Alzheimer’s Disease From the Perspective of Pathophysiological Processes

Presently, there is a lack of effective disease-modifying drugs for the treatment of Alzheimer’s disease (AD). Uncaria rhynchophylla (UR) and its predominant active phytochemicals alkaloids have been studied to treat AD. This study used a novel network pharmacology strategy to identify UR alkaloids against AD from the perspective of AD pathophysiological processes and identified the key alkaloids for specific pathological process. The analysis identified 10 alkaloids from UR based on high-performance liquid chromatography (HPLC) that corresponded to 127 targets correlated with amyloid-β (Aβ) pathology, tau pathology and Alzheimer disease pathway. Based on the number of targets correlated with AD pathophysiological processes, angustoline, angustidine, corynoxine and isocorynoxeine are highly likely to become key phytochemicals in AD treatment. Among the 127 targets, JUN, STAT3, MAPK3, CCND1, MMP2, MAPK8, GSK3B, JAK3, LCK, CCR5, CDK5 and GRIN2B were identified as core targets. Based on the pathological process of AD, angustoline, angustidine and isocorynoxeine were identified as the key UR alkaloids regulating Aβ production and corynoxine, isocorynoxeine, dihydrocorynatheine, isorhynchophylline and hirsutine were identified as key alkaloids that regulate tau phosphorylation. The findings of this study contribute to a more comprehensive understanding of the key alkaloids and mechanisms of UR in the treatment of AD, as well as provide candidate compounds for drug research and development for specific AD pathological processes.

Effect of Uncaria rhynchophylla against Thioacetamide-Induced Acute Liver Injury in Rat

Both oxidative stress (OS) and inflammation are two fundamental pathological processes of acute liver injury (ALI). The current work is to investigate the effect and possible mechanism of Uncaria rhynchophylla (UR) on thioacetamide- (TAA-) induced ALI in rats. UR (100 and 200 mg/kg) was orally administrated with TAA (200 mg/kg of bodyweight, intraperitoneal injection) for 3 consecutive days. ALI was confirmed using histological examination and the factors associated with OS and liver function activity measured in serum. Moreover, expressions of inflammation and collagen-related proteins were measured by the Western blot analysis. Myeloperoxidase (MPO), which mediates OS in the ALI control group, was manifested by a significant rise compared with the normal group. UR significantly reduced AST, ALT, and ammonia levels in serum. The nuclear factor-κB (NF-κB) activation induced by TAA led to increase both inflammatory mediators and cytokines. Whereas, UR administration remarkably suppressed such an overexpression. UR supplementation improved matrix metalloproteinases (MMPs) such as MMP-1, -2, and -8. In contrast, tissue inhibitors of metalloproteinases- (TIMP-) 1 level increased significantly by UR treatment. In addition, the histopathological analysis showed that the liver tissue lesions were improved obviously by UR treatment. UR may ameliorate the effects of TAA-induced ALI in rats by suppressing both OS through MPO activation and proinflammatory factors through NF-κB activation. In conclusion, UR exhibited a potent hepatoprotective effect on ALI through the suppression of OS.

In Vitro Antibacterial Activities of the Tibetan Herbal Medicines Against the Staphylococcus Isolated From Mastitis of Guanzhong Dairy Goat

Background: Dairy goat mastitis is one of the most significant disease with effect on Guanzhong dairy goat breeding. The purpose of this study was to screen the pathogenic bacteria from milk samples of the mastitis of Guanzhong dairy goat and evaluate the antibacterial activities of six Tibetan herbal medicines, including Swertia bimaculata, Gentiana urnula, Uncaria rhynchophylla, Aconitum flavum, Dracocephalum tanguticum and Lagotis brachystachy on Staphylococcus isolated. Results: Fifty-two bacteria species, and a total of 149 different isolates were identified from 55 milk samples, and Staphylococcus was the predominant species as it accounted for 36.91% (55/149) of the identified isolates, and S. aureus (26/55) was the majority of the Staphylococcus isolates. Histopathological examination showed that obvious pathological changes were observed in the liver, kidney and lung tissues of the mice infected with S. aureus. Most of the Staphylococcus isolates expressed the multidrug resistance except for S. aureus and S. hemolyticus. The water extracts of several Tibetan medicinal plants exhibited distinguished in vitro antibacterial activities for the Staphylococcus, especially the S. aureus as well as the MDR isolates. Lagotis brachystachy has the most significant antibacterial activity, and followed by the Aconitum flavum, Uncaria rhynchophylla, Swertia bimaculata, and Dracocephalum tanguticum, while the Gentiana urnula showed the weaker inhibitory effects to the tested Staphylococcus isolates. Conclusion: This study indicated that Tibetan herbal medicines could be a potential candidate for the treatment the mastitis of dairy goat in clinical application.