Bavachin enhances NLRP3 inflammasome activation induced by ATP or nigericin and causes idiosyncratic hepatotoxicity / 医学前沿

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.

Erratum: Author correction to 'Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome' Acta Pharmaceutica Sinica B 9 (2019) 734-744

[This corrects the article DOI: 10.1016/j.apsb.2019.02.003.].

Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome

Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin (CDN), the major active ingredient of the traditional Chinese medicinal herb , has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-B-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner. Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1 production induced by LPS , which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.

Analysis of the preventive and therapeutic effects of Taohe Chengqi decoction on a rat model of hepatic encephalopathy / 中国比较医学杂志

Objective To analyze the preventive and therapeutic effects of a traditional Chinese medicine Taohe Chengqi decoction on a rat models of hepatic encephalopathy ( HE) induced by thioacetamide ( TAA) .Methods The rat model of HE was established by intraperitoneal injection of TAA,and the effects of Taohe Chengqi decoction were observed by neurobehavioral changes,neurological test,blood ammonia,serum biochemical indexes,and liver and brain pathological examination.Results The rat model of hepatic encephalopathy was successfully established.Low, medium and high dose Taohe Chengqi decoction markedly improved neuro-reflexes and liver and brain pathological damages, and significantly decreased the HE staging and serum biochemical indexes, and the results of high dose group was the best, similar to that of positive drug-treatment group.Conclusions Taohe Chengqi decoction exhibits promising preventive and therapeutic effects on the rat model of TAA-induced hepatic encephalopathy, and these results provide substantial experimetal evidence for its clinical application.

Effects of resveratrol on blood pressure and cardiac function in the rats with vascular calcification / 中国比较医学杂志

Objective To observe the effects of resveratrol on blood pressure and cardiac function in the rats with vascular calcification induced by vitamin D3 plus nicotine.Methods 32 male SD rats were randomly divided into the following groups for treatment:Control (Con), calcified (Cal), Cal+Res low dose [L] and Cal+Res high dose [H] groups.Blood pressure, cardiac function, alkaline phosphatase ( ALP ) activity in serum or aorta were detected and HE staining was used for pathological examination at 6 weeks after treatment.Results Compared with the Con group, LVW/BW, heart rate, systolic aortic pressure, pulse pressure, mean blood pressure, left ventricular systolic pressure and ALP activity in serum or aorta of rats in the Cal group were increased by 27.3%, 8.8%, 22.8%, 47.5%, 13.6%, 19.0%, 280%and 265%( P<0.05 or P<0.01) , respectively.Compared with the Cal group, pulse pressure and ALP activity in serum or aorta of rats in the Cal+Res [L] group were decreased by 8.5%, 34.5%and 29.5%(P<0.05 or P<0.01), respectively, and LVW/BW, systolic aortic pressure, pulse pressure, mean blood pressure, left ventricular systolic pressure and ALP activity in serum or aorta of rats in the Cal +Res [ H] group were decreased by 14.2%, 13.6%, 23.7%,10.0%, 9.0%, 53.1%and 45.9%(P<0.05 or P<0.01), respectively.Compared with the Cal+Res [L] group, systolic aortic pressure, pulse pressure, left ventricular systolic pressure and ALP activity in serum or aorta of rats in the Cal+Res [H] group were decreased by 8.3%, 16.7%, 5.8%, 28.4% and 23.2% (P<0.05 or P<0.01), respectively.Compared with the aorta in the Con group, pathological examination revealed thickened vessel walls and disordered elastic fibers in the calcified aortas.However, the thickness of aortic wall in the Cal+Res [ L] and Cal+Res [ H] groups was reduced and elastic fibers were regularly arranged.Conclusion Resveratrol can effectively reduce the blood pressure and improve the cardiac function in rats with vascular calcification.

Thinking and practice of animal ethology in study of cold and hot nature of traditional Chinese medicine / 中国中药杂志

From the view of macroscopic animal ethology combined with computer and modem image processing technique, by monitoring the temperature tropism of animal affected by traditional Chinese medicine (TCM) with different Cold and Hot natures and obtaining many behavior parameters which were difficult to assess in direct observation, the differences between the Cold and Hot nature of TCM were evaluated and presented. This method could real-time, intuitively and objectively, qualitatively and quantitatively monitor the temperature tropism of experimental animals with no disturbance. Further, the Cold and Hot nature of TCM can be expressed from the whole animal level. This method met to the application peculiarity of TCM and suited for the TCM theoretical system. It is a attempt for the study of drug nature of TCM. It also contributed to elucidate the objective authenticity and scientific connotation of Cold and Hot nature of TCM, and express the inherent connection of this nature and the temperature tropism of animal. In this review, a new point and technology platform was provided for establishing an objective method for evaluating the Cold and Hot nature of TCM, which are corresponding with the feature of the application of TCM.

COLD or HOT natural attribute of Zuojinwan and Fanzuojinwan based on temperature tropism of mice / 药学学报

This study is to investigate the authenticity between COLD and HOT natural attribute in the famous Chinese medicine formulas--Zuojinwan (Coptis-Evodia 6 : 1) and Fanzuojinwan (Coptis-Evodia 1 : 6) based on mice temperature tropism, and establish an objective method to estimate the difference of two natural attribute by using a cold/hot plate differentiating technology. The results indicated that the COLD nature Zuojinwan could decrease significantly the remaining rate of HOT-symptom rat on warm pad (P < 0.05). That was not notable to COLD-symptom rat. The interference result of COLD-HOT temperature tropism to COLD/HOT symptom rat in Fanzuojinwan was the reverse with the COLD nature Zuojinwan. Meanwhile, biochemical indicators which are relative to energy metabolism such as ATPase enzyme activity and total anti-oxidant capability (T-AOC), had corresponding change in the organism. In the study, the COLD and HOT natural tendency in Zuojinwan and Fanzuojinwan which were composed by the same herbs with different proportion could be expressed qualitatively, quantitatively, objectively and directly with applying animal temperature tropism, and be verified to philosophical idea of treating disease theory with "expelling heat with cold herbs and cryopathy requiring warm prescription", not "expelling heat with heat herbs and cryopathy requiring cold prescription" in ancient traditional Chinese medicine, which brings a new approach in investigation of the nature theory of traditional Chinese medicine.

Investigation of differences between cold and hot nature of Mahuang decoction and Maxing Shigan decoction based on cold/hot plate differentiating assay / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the objectivity and authenticity of the difference of the Cold and Hot nature between Mahuang decoction and Maxingshigan decoction based on the cold/hot plate differentiating assay.</p><p><b>METHOD</b>The measuring time and dosage of Mahuang decoction and Maxingshigan decoction were investigated before the compliance experiment. Meanwhile, the activities of adenosine triphosphatase were detected in order to probe into the mechanism of their action.</p><p><b>RESULT</b>It was found that the drug dose should be 10 times amount to human dose (0.80 g x kg(-1) of Mahuang decoction and 2.26 g x kg(-1) of Maxing Shigan decoction) and the measuring time should be from 30 min to 60 min after administering. Compared with the control group, the remaining ratio of the mice treated with Mahuang decoction on the hot pad significantly decreased (P < 0.01). Compared with Mahuang decoction, the remaining ratio of the mice treated with Maxingshigan decoction on the hot pad significantly increased (P < 0.05). Compared with the control group, the Na(+) -K(+) -ATPase activity of liver tissue of the mice treated by Mahuang decoction significantly increased (P < 0.05), while the activity of Na(+) -K(+) -ATPase and Mg(2+) -Ca(2+) -ATPase of liver tissue of the mice treated by Maxingshigan decoction reduced significantly (P < 0.05).</p><p><b>CONCLUSION</b>This study showed that the differences of Cold and Hot nature of Mahuang decoction and Maxingshigan decoction were objectively existent from animal ethology, which was consistent with the traditional theroy of Chinese medicine. And the changes of ATPase activity of liver tissue might be the mechanism of drug action.</p>