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.

Large dose means significant effect--dose and effect relationship of Chi-Dan-Tui-Huang decoction on alpha-naphthylisothiocyanate-induced cholestatic hepatitis in rats.

BACKGROUND: Large dose application of traditional Chinese medicines has attracted more and more attentions in recent years. However, the scientific connotation of large dose application has not been clarified so far. The present study was designed to investigate the protective effects of Chi-Dan-Tui-Huang decoction (CDTHD) against Alpha-naphthylisothiocyanate (ANIT) induced acute cholestatic hepatitis in rats and explore the dose-effect relationship of CDTHD as a reference for clinical application. METHODS: The administration of CDTHD at a series of doses was performed twice each day for 5 days. The acute cholestasic hepatitis models were induced by intragastric administration of ANIT on the third day of CDTHD administration. Then, the protective effects on cholestatic hepatitis were investigated by examining the following parameters: body weights of rats, morphological and histopathological liver changes, the levels of serum biomarkers including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin and γ-glutamyltranspeptidase. Furthermore, the dose-effect relationship was investigated with the application of correspondence analysis. RESULT: In the tested range of doses, CDTHD at the maximum tolerance dose did not show any toxicity as time went on. The efficacy result showed that CDTHD from 21.6 g/kg⋅d to 86.4 g/kg⋅d exhibited significant hepatoprotective effect against ANIT-induced acute cholestatic hepatitis. It alleviated liver injury and reversed adverse biochemical and histopathological changes in a dose-dependent manner. Correspondence analysis showed that Radix Paeoniae Rubra in CDTHD was the main effective component and CDTHD could enhance the integrated efficacy in dose-dependent manner. CONCLUSIONS: CDTHD is beneficial to liver protection in a dose-dependent manner. Especially large dose demonstrates potent efficacy and Radix Paeoniae Rubra in the formula contributes the main effect on ANIT-induced acute cholestatic hepatitis without toxicity.

[Rationality of the processing methods of aconiti lateralis radix (Fuzi) based on chemical analysis].

In this study, we explored the rationality of processing methods and mechanism of Aconiti Lateralis Radix (Fuzi) through comparing the chemical contents of diester alkaloids (DAs) and monoester alkaloids (MAs) in the raw material of Fuzi and its processed products. The results showed that the toxicity potency of MAs is at least lower than 1/64 to 1/180 of the toxicity potency of DAs. The contents of DAs in processed Fuzi decreased to 1/76.5 to 1/38.3 of the value of raw Fuzi. The contents of MAs in processed Fuzi significantly increased by 4.6 to 5.2 fold or basically the same as that of the raw Fuzi. The values of MAs/DAs of processed Fuzi were enhanced by 30 to 390 fold of the raw Fuzi. It was found that the contents of DAs were insignificantly different between "Wu dan fu pian" (steaming or stir-frying without Danba) and "Dan fu pian" (steaming or stir-frying with Danba). The result suggested that the abilities of "eliminating toxicity" of different processing methods were equivalent at all. In contrast, the contents of MAs contained in "Wu dan fu pian" were of 5.3 to 8.7 fold higher than the values in "Dan fu pian". This result suggested the processing method by steaming or stir-frying without Danba might have better effect for "conserving property" than the method processed with Danba stipulated by China Pharmacopoeia. We believe that the new processing method without Danba can be recommended in further application due to it offers a simple procedure and it will not introduce inorganic impurities in the products.