Leeches attenuate blood hyperviscosity and related metabolic disorders in rats differently than aspirin.

ETHNOPHARMACOLOGICAL RELEVANCE: Whitmania pigra Whitman (Whitmania pigra, WP), firstly recorded in the Shennong's Herbal Classic and officially listed in the Chinese Pharmacopoeia, is a well-used cardiovascular protective traditional Chinese medicine derived from leeches. Traditional Chinese physicians prefer to prescribe the dried whole body of leech processed under high temperatures. It has been reported that dried WP remains clinically effective. However, the therapeutic mechanism has yet not be clearly elucidated. AIM OF THE STUDY: This study was designed to investigate the protective activity of the extract of WP in a high-molecular-weight dextran-induced blood hyperviscosity rat model, and to explore the role of WP in improving blood hyperviscosity related metabolic disorders and to clarify the possible mechanism of metabolic regulation. MATERIALS AND METHODS: The hemorheological parameters were measured with an automated blood rheology analyzer. Hematoxylin-eosin staining was used to observe the pathological changes in aortic tissues samples. Further, a liquid chromatography-mass-spectrometry (LC-MS)-based untargeted metabolomics approach was applied to characterize the metabolic alterations. RESULTS: WP has evident attenuating effects on blood hyperviscosity and related metabolic disorders, and the influences are distinct from those of aspirin. The results showed that WP had good effects in reducing blood viscosity and ameliorating histopathological changes in the thoracic aorta in a high molecular weight dextran-induced blood hyperviscosity rat model. The middle dose (2.5 g raw material/kg body weight) of WP exhibited effects equivalent to aspirin (100 mg/kg) on hemorheological and histopathological parameters (P > 0.05). However, when using metabolomics profiling, we found that WP could significantly improve blood hyperviscosity-related metabolic disorders and restore metabolites to normal levels; while aspirin showed little effect. With principal component analysis and orthogonal partial least-squares discriminant analysis, WP regulated many more endogenous metabolites than aspirin. With pathway enrichment analysis, the differential endogenous metabolites were involved in cysteine and methionine metabolism, TCA cycle, arachidonic acid metabolism, etc., highlighting the metabolic reprogramming potential of WP against blood hyperviscosity-induced metabolic disorders. CONCLUSIONS: The study suggest that WP has a more potent effect, but a different mechanism, than aspirin in improving either blood hyperviscosity or related metabolic disorders associated with cardio- and cerebrovascular diseases.

Anti-inflammatory and Analgesic Effects of Polygonum orientale L. Extracts.

Background and Purpose:Polygonum orientale L. (family: Polygonaceae), named Hongcao in China, is a Traditional Chinese Medicinal and has long been used for rheumatic arthralgia and rheumatoid arthritis. However, no pharmacological and mechanism study to confirm these clinic effects have been published. In this investigation, the anti-inflammatory, analgesic effects and representative active ingredient compounds of P. orientale have been studied. Methods: Dried small pieces of the stems and leaves of P. orientale were decocted with water and partitioned successively to obtain ethyl acetate and ethyl ether extract of P. orientale (POEa and POEe). Chemical compositions of them were analyzed by UPLC-Q-Exactive HRMS. Anti-inflammatory and analgesic effects of POEa and POEe were evaluated using xylene induced ear edema, carrageenan induced paw edema, Freunds' complete adjuvant induced arthritis, and formaldehyde induced pain in rat. Their mechanisms of anti-inflammatory and analgesic effects were also studied via assays of TNF-α, IL-1ß, IL-6, and PGE2 in serum. Results: UPLC-Q-Exactive HRMS analysis showed that POEa and POEe mainly contained flavonoids including orientin, isoorientin, vitexin, luteolin, and quercetin. Furthermore, anti-inflammatory effects of POEa and POEe were evident in xylene induced ear edema. The paw edema in Freund's complete adjuvant and carrageenan were significantly (P < 0.05, 0.01) inhibited by POEa (5, 7.5 g/kg). POEe (7.5 g/kg) was significantly (P < 0.05, 0.01) inhibited Freunds' complete adjuvant induced paw edema and cotton pellet induced granuloma formation. Similarly, POEe significantly (P < 0.05, 0.01) inhibited the pain sensation in acetic acid induced writhing test. POEa (5, 7.5 g/kg) significantly (P < 0.05, 0.01) inhibited formaldehyde induced pain in both phases. POEa (7.5 g/kg) markedly (P < 0.05) prolonged the latency period of hot plate test after 30 and 60 min. The concentrations of TNF-α, IL-1ß, IL-6, and PGE2 were significantly (P < 0.01) decreased by POEa (3.75, 5 g/kg). Conclusion: POEa and POEe have anti-inflammatory and analgesic effects, which was mainly relevant to the presence of flavonoids, including orientin, isoorientin, vitexin, luteolin, and quercetin. The mechanism of anti-inflammatory and analgesic effects of POEa may be to decrease the concentrations of TNF-α, IL-1ß, IL-6, and PGE2 in serum.