Panax Notoginseng Saponins Alleviate LPS-induced Fibrosis of HK-2 Cells by Inhibiting the Activation of NLRP3 Inflammasome and Pyroptosis.

BACKGROUND: Renal fibrosis is related to impaired kidney function and can eventually lead to end-stage renal disease, for which no effective treatment is available. Panax notoginseng saponins (PNS), as a commonly used traditional Chinese medicine, is considered a possible alternative for the treatment of fibrosis. OBJECTIVE: The purpose of the present study was to investigate the effects and possible mechanisms of PNS on renal fibrosis. METHODS: HK-2 cells were used to induce renal fibrosis cell model by lipopolysaccharide (LPS), and the cytotoxicity of PNS on HK-2 cells was investigated. Cell damage, pyroptosis, and fibrosis were analyzed to investigate the effects of PNS on LPS-induced HK-2 cells. NLRP3 agonist Nigericin was used further to explore the inhibitory effect of PNS on LPS-induced pyroptosis so as to clarify the possible mechanism of PNS on renal fibrosis. RESULTS: PNS had no cytotoxicity on HK-2 cells, and could reduce the apoptosis and the release of lactate dehydrogenase (LDH) and inflammatory cytokines of LPS-induced HK-2 cells, showing an alleviating effect on cell damage. PNS also reduced the expression of pyroptosis proteins NLRP3, IL-1ß, IL-18, and Caspase-1, as well as fibrosis proteins α-SMA, collagen Ⅰ and p-Smad3/Smad3, which showed an inhibitory effect on LPS-induced pyroptosis and fibrosis. In addition, LPS-induced cell damage, pyroptosis, and fibrosis were aggravated after Nigericin treatment, while PNS alleviated the aggravation caused by Nigericin. CONCLUSION: PNS inhibits pyroptosis by inhibiting the activation of NLRP3 inflammasome in LPS-induced HK-2 cells, which ultimately alleviates renal fibrosis and plays a good role in the treatment of kidney diseases.

An Objective Diagnosis Model with Integrated Metabolic and Immunity Parameters for Phlegm-Dampness Constitution.

BACKGROUND: According to Chinese constitutional theory, people can be divided into nine constitutions, which represent distinctive vulnerability to different diseases such as metabolic syndrome, atherosclerosis, and immunity-related disease, and so forth in modern medicine, phlegm-dampness constitution (PDC) is one of the nine constitutions, which is susceptible to metabolic syndrome (MS) and atherosclerosis that associate with lipid metabolism and immunity dysregulation closely. OBJECTIVES: In this study, we aimed to investigate the metabolic and immunity profiles of phlegm-damp constitution (PDC), including metabolites, lymphocytes distribution, and inflammatory cytokines. METHODS: A total of 74 patients with PDC and 66 individuals with gentle constitution (GC) were enrolled in this study. We utilized biochemical methods to detect metabolic parameters, flow cytometry to survey T/B/NK/NKT lymphocyte subgroups distribution, and ELISA to assay inflammatory cytokines. RESULTS: The subjects with PDC had higher GLU, AI TC, TG, and LDL-C and lower HDL-C levels. The immunity profile indicated that PDC subjects had higher percentage of WBCs, neutrophils, lymphocytes, B cells, and natural killer T cells compared with subjects with GC (P < 0.05). Serum levels of IL-10 decreased significantly in the subjects with phlegm-damp constitution, whereas IL-12 levels increased dramatically in the PDC group compared with the GC group (both P < 0.05). Additionally, logistic regression identified four independent variables (GLU, TG, LDL-C, and lymphocytes) that were highly correlated with PDC (P < 0.05). The area under the curve of the receiver operating characteristic curve was 0.878, which indicated the data were reliable to distinguish the subjects with PDC from the ones with GC. CONCLUSION: Phlegm-damp constitution was prone to hyperglycemia and hyperlipidemia syndrome, promoting the occurrence and progression of metabolic-related diseases. Interestingly, proinflammatory cells and cytokines were activated in the PDC group as well. Our findings could offer a profile of early screening indicators to identify high-risk patients of metabolic- and immunity-related diseases from Chinese constitution.

[Generalized science of Chinese material medica-from preventive treatment of disease to Chinese medicine health industry].

Based on the systematic summary of the results of the fourth general survey of traditional Chinese medicine resources, the cultivation of large varieties of Chinese material medica and the latest research on health industrial development, the novel concepts and scientific connotations of generalized science of Chinese material medica are put forward, and the basic ideas and methods of a new Chinese medicine academic system, the cultivation system of large varieties of Chinese medicinal materials and the application system of the large health industry are constructed. This kind of generalized science of Chinese material medica, rooted in the traditional Chinese culture and the theory of "preventive treatment of disease", can avoid the narrow prospect induced by the increasing specialization and refinement of knowledge of science of Chinese material medica. It will play an important role in the modernization, industrialization, internationalization of traditional Chinese medicine.

[New method for evaluating pharmacodynamics of traditional Chinese medicine compounds based on its moderate regulation and principle of balanced adjustment of immunity under pan-immunomic].

For the basic research on the traditional Chinese medicine(TCM), objective syndrome of traditional Chinese medicine and evaluation criteria of traditional Chinese medicine compounds are hardly to break though. While, the modern immunology points out that the body is a counterbalance state and immune imbalance is the root of sickness. The thinking mode of treating diseases in traditional Chinese medicine is also "balance", considering disease is the result of bias which present the imbalance of "Yin counters Yang", "exterior counters interior", "cold counters heat" and "weak counters strong". The Chinese herbal compound formula preparation was applied on disease therapy based on theory of Chinese medicine, which was confirmed by long period clinical application. It is composed of multi-compounds and has the characteristic of multi-targeting. Integrative medicine has spawned pan-immunomics, and the evaluation of immune function (immune balance) has become an important basis for diagnosis and treatment models of integrative medicine. In addition, balance is the core idea of whole-systemic conception of traditional Chinese medicine. Therefore, we speculate that immune balance under pan-immunomic can bridge the traditional Chinese medicine and modern integrative medicine and is the important basis for objective syndrome of traditional Chinese medicine and evaluation criteria of traditional Chinese medicine compounds. According to the bridging theory, we attempt to utilize informatics and statistical methods to construct an evaluation system for pharmacodynamics of traditional Chinese medicine based on its moderate regulation and the balanced adjustment of immunity under pan-immunomic, which further reveal the scientific essence of the whole-systemic view of traditional Chinese medicine. This research brings out a new valuable strategy and provides a theoretical basis for accelerating the transformation of traditional Chinese medicine, especially the exploitation of Chinese herbal compound formula, and constructing the new drug innovation and review system for traditional Chinese medicine. Besides as a reference for traditional Chinese medicine objective syndrome and pharmacodynamics of traditional Chinese medicine compounds, the evaluation system can screen the immunity of sub-health population also. With the continuous accumulation of clinical sample and data, the evaluation system will be more accurate and intelligent.