[Effect of C21 steroidal glycoside of Cynanchum auriculatum on liver and kidney fibrosis through TLR4 pathway].

The liver and kidney fibrosis model was established by thioacetamide(TAA) and unilateral ureteral obstruction(UUO) in SD rats. The rats were randomly divided into three groups: model group, low and high-dose groups of C21 steroidal glycosides of Cynanchum auriculatum. Another blank control group was set. Four weeks later, serum was taken to detect the biochemical indexes of liver and kidney function. Urine protein and urine creatinine were detected by kits. Liver and kidney tissue samples were stained with HE and Masson staining, and hydroxyproline content was detected. Western blot was used to detect expressions of fibrotic proteins, inflammatory factors and TLR4 signaling pathways, so as to observe the preventive and therapeutic effects of C21 steroidal glycosides from C. auriculatum on hepatic and renal fibrosis and explore its molecular mechanism. Four weeks later, serum biochemical results showed that liver and kidney functions were seriously damaged, and pathological sections showed that inflammatory cell infiltration, decrease of parenchymal cells, and increase of interstitial fibrosis in liver and kidney tissues. The results showed that low and high doses(150, 300 mg·kg~(-1)) of C21 steroidal glycosides could significantly reduce the collagen deposition and the pathological changes of liver and kidney fibrosis compared with the model group. At the same time, we found that the expression levels of TLR4 and MyD88 signaling pathway proteins were significantly increased in the liver and kidney tissues of the model group, and a large number of NF-κB signaling pathway proteins migrated into the nucleus. On the contrary, the expression levels of TLR4, MyD88 signaling pathway proteins and the nuclear migration of NF-κB were significantly inhibited in the low and high dose groups of C21 steroidal glycosides from C. auriculatum. Therefore, it was speculated that the mechanism of C21 steroidal glycoside for preventive and therapeutic effect on hepatic and renal fibrosis was related to inhibit TLR4/MYD88/NF-κB inflammatory pathway, thus preventing hepatic and renal fibrosis.

Less SO2 residue may not indicate higher quality, better efficacy and weaker toxicity of sulfur-fumigated herbs: Ginseng, a pilot study.

Sulfur dioxide (SO2) is a hazardous residue in sulfur-fumigated herbs. Standards limiting SO2 content have been adopted worldwide for quality control of sulfur-fumigated herbs, and herbs with less SO2 are believed to be better. However, the standards are based only on the safe dose of SO2 and may not characterize changes in herbal quality, thereby the efficacy and toxicity, resulting from sulfur fumigation. To confirm this, here the correlation of residual SO2 content with the quality/efficacy/toxicity of sulfur-fumigated herb was investigated, and ginseng was selected as a pilot study object. Four sulfur-fumigated ginseng samples with different SO2 contents were systemically compared regarding their quality, anti-inflammatory, anti-shock and anti-stress efficacies, as well as acute and chronic toxicities. The results demonstrated that the SO2 content did not correlate with the quality, efficacy and toxicity changes of ginseng; more specifically, less SO2 residue did not indicate higher quality, better efficacy nor weaker toxicity. This fact suggests that SO2 content cannot characterize the variations in quality, efficacy and toxicity of sulfur-fumigated herbs. Therefore, the standard limiting SO2 content alone may be inadequate for quality control of sulfur-fumigated herbs, and new standards including other indicators that can exactly reflect herbal efficacy and safety are necessary.

Effects of sulfur-fumigation on the pharmacokinetics, metabolites and analgesic activity of Radix Paeoniae Alba.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Paeoniae Alba (Baishao, BS), one of the most commonly used traditional Chinese medicinal herbs, has many pharmacological effects including analgesic activity. Previous studies found that sulfur-fumigation, a post-harvest handling process developed to prevent mold contamination of medicinal herbs, altered the quality of BS. However, whether sulfur-fumigation affects the pharmacokinetics, safety and efficacy of BS warrants further investigation. AIM OF THE STUDY: To evaluate the feasibility of sulfur-fumigation as a post-harvest handling process of BS from the viewpoints of pharmacokinetics, safety and efficacy. MATERIALS AND METHODS: The pharmacokinetic behaviors of four active components of BS and one characteristic component of sulfur-fumigated BS (S-BS) were evaluated by high performance liquid chromatography triple quadrupole mass spectrometry (HPLC-TQ-MS/MS). The safety was investigated using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) based metabolomics approach after intragastric (i.g.) administration of non-fumigated BS (N-BS) and S-BS in rats. The analgesic efficacy was compared using hot-plate test in mice, after i.g. administration of N-BS and S-BS, at both high and low dosages. RESULTS: Systemic exposures of paeoniflorin and oxypaeoniflorin, two analgesic components of BS, were significantly decreased in the S-BS treated group compared to the N-BS treated group, while paeoniflorin sulfonate, one of the sulfur-containing derivatives of S-BS, was detected in all time-points of S-BS treated group with the area under the plasma concentration-time curve (AUC0-t) and the maximum plasma concentration (Cmax) as high as 7077.06 ± 2232.97ng/mL*h and 1641.42 ± 634.79ng/mL respectively, which indicated that sulfur-fumigation altered the pharmacokinetic behaviors of BS. Besides, paeoniflorin sulfonate and its four metabolites with ambiguous toxicities, as well as one endogenous metabolite p-cresol glucuronide, the biomarker of disordered homeostasis of intestinal bacteria and bile acid, were identified as the characteristic metabolites in S-BS administered rats, suggesting that sulfur-fumigation reduced the safety of BS. Furthermore, the analgesic effects at both low and high dosages were decreased in different extent when compared to N-BS administered groups, indicating that sulfur-fumigation weakened the efficacy of BS. CONCLUSION: Sulfur-fumigation altered the pharmacokinetics, as well as reduced the safety and efficacy of BS, suggesting that sulfur-fumigation is not recommended for post-harvest handling of BS.

Gualou Xiebai Decoction prevents myocardial fibrosis by blocking TGF-beta/Smad signalling.

OBJECTIVES: The present study is aimed to investigate the effect of Gualou Xiebai Decoction (GXD) ethanol extract on myocardial fibrosis and clarify the possible mechanism. METHODS: Rats with ligated left anterior descending coronary artery were treated with GXD ethanol extract (1.14 g/kg, 2.27 g/kg, 4.53 g/kg) daily via gavage for 4 weeks. Histopathological changes and collagen distribution were evaluated by haematoxylin and eosin and Masson staining. The mRNA levels of Collagen I and Collagen III were detected by real-time PCR. The expressions of TGF-ß1, TGFß receptor (TGFßR)I, TGFßRII, P-Smad2/3 and Smad7 were determined by Western blot. RESULTS: GXD treatment was significantly reduced the heart weight/body weight ratio (P < 0.05) as well as the left ventricle weight/body weight ratio (P < 0.05). It also significantly alleviated the degree of inflammation, decreased myocardial collagen volume fraction (P < 0.05 ∼ 0.01), together with markedly prevented the upregulations of Collagen I and Collagen III (P < 0.05 ∼ 0.01). Moreover, GXD downregulated expressions of TGF-ß1, TGFßRI, TGFßRII, Smad2/3 whereas improved Smad7 expression in the myocardial fibrosis rats. CONCLUSIONS: GXD ameliorates myocardial fibrosis induced by cardiac infarction with ligated left anterior descending coronary artery, the mechanism maybe involve in inhibiting the TGF-ß1 signalling pathway.

[Study on Cornu Bos grunniens from Tibet substituting Cornu Rhinoceri].

OBJECTIVE: Comparing the pyretolysis effect of Cornu Rhinoceri Soup, an ancient prescription of Traditional Chinese Medicine, on fever model of rabbits after Cornu Bos grunniens from Tibet substituting Cornu Rhinoceri, in order to find the succedaneums of Cornu Rhinoceri, a rare animal medicine. METHODS: The fever model was made by over-due Triple-Vaccine i.v. through the vein of rabbit in edge ear. 1 hour later, the different decoctions i.g. in different groups of rabbits, then detecting the dynamic changes of body temperature in fever rabbits. RESULTS: 1 hour after the decoction i.g., there were significant pyretolysis effects in the Cornu Bos grunniens groups of rabbits with large and small dosage (P < 0.05 or 0.01). After 2h,the same effect showed in the Cornu Bubali group with large dosage (P < 0.05 or 0.01) and 3h later in small one. In the groups of Cornu Rhinoceri, large dosage i.g. 1 h later, the rising amplitude of body temperature in fever rabbits was slower comparing to the model group. 2h later, there were the same effects as other groups. CONCLUSION: The pyretolysis effect of Cornu Rhinoceri Soup on fever model rabbits is as same as it of which containing Cornu Bos grunniens instead of Cornu Rhinoceri. It means that the Cornu Bos grunniens from Tibet could be the substitution of Cornu Rhinoceri.