Effect of Isodon ternifolius-medicated serum on hepatic stellate cells based on TLR4/NF-κB/NLRP3 signaling pathway / 中国中药杂志

The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type Ⅰ collagen(COL Ⅰ), COL Ⅲ, transforming growth factor-β1(TGF-β1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL Ⅰ, COL Ⅲ, α-SMA, TGF-β1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.

Correlation and Traditional Chinese Medicine Intervention of Pyroptosis and Liver Diseases / 中国实验方剂学杂志

Pyroptosis， also known as cell inflammatory necrosis， is different from apoptosis， necrosis， and other forms of cell death in morphological characteristics， occurrence， and regulatory mechanism. It is a new type of programmed cell death dependent on Caspase， which has been discovered and confirmed in recent years. Studies have shown that pyroptosis is closely related to the occurrence of liver diseases， and is critical in alcoholic liver disease （ALD）， non-alcoholic fatty liver disease （NAFLD）， liver fibrosis， and liver cancer. Pyroptosis causes inflammatory injury of hepatocytes to promote the occurrence and development of liver diseases by activating Caspase-1， cleaving the effector gasdermin-D （GSDMD）， and releasing pro-inflammatory cytokines， such as interleukin-18 （IL-18） and interleukin-1β （IL-1β） mainly through the classical NOD-like receptor protein 3 （NLRP3） inflammasome pathway. Clinically， Chinese medicine in the treatment of liver diseases has unique efficacy and low side effects. In the intervention on liver diseases， Chinese medicine blocks the pyroptosis signaling pathway to relieve the liver inflammation by inhibiting the assembly and activation of NLRP3 inflammasome multiprotein complex， blunting the activity of Caspase-1 or Caspase-4/Caspase-5/Caspase-11， and inhibiting the cleavage of GSDMD to reduce the release of pro-inflammatory cytokines such as IL-18 and IL-1β. Therefore， in-depth investigation of pyroptosis facilitates unveiling its role in the occurrence， development， and prognosis of liver diseases， and the enhancement or inhibition of pyroptosis may provide a new strategy for the prevention and treatment of liver diseases by Chinese medicine. At present， NLRP3 inflammasome， a key protein in the classic pyroptosis signaling pathway， has become an anti-liver disease target of Chinese medicine. This study briefly summarized the relationship between pyroptosis and liver diseases and reviewed the intervention of monomers， compound prescriptions， effective fractions and extracts of Chinese medicine in recent years to provide important guidance for further exploring the pathogenic mechanism of pyroptosis and the treatment of liver diseases with Chinese medicine.

Research Progress of Blood Brain Barrier Model and Effect of Traditional Chinese Medicine on Its Permeability / 中国实验方剂学杂志

Blood brain barrier (BBB), as barrier between plasma and brain cells formed by brain capillary wall and glial cells and barrier between plasma and cerebrospinal fluid formed by choroid plexus, can prevent some brain tissues (mostly harmful substances), so as to maintain a stable internal environment of brain tissues, while stopping most drugs from the intracranial and causeing difficulties to cerebral diseases. The establishment of experimental model of BBB is a key technique for drug treatment of craniocerebral diseases. Therefore, the establishment of the BBB model and the study of its permeability change will deepen the understanding of the neuro-vascular interaction and provide an important theoretical basis for the diagnosis and treatment of central nervous system diseases. Traditional Chinese medicine(TCM) can affect brain tissue superoxide dismutase (SOD) activity, inhibit myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) content, so as to affect the expression of zonula occluden-1 (ZO-1) or up-regulate the expression of Claudin-5, inhibit BBB permeability under pathological conditions, and play a protective role in BBB. TCM can also promote the changes in BBB permeability by affecting the expressions of cell adhesion factor-1 (CAM-1), ZO-1, filamentous actin(F-actin), P-glycoprotein(P-gp)and 5-hydroxytryptamine (5-HT), or increase drug permeability through co-delivery with other drugs. In this paper, the methods, advantages and disadvantages of the establishment of experimental models of the BBB in recent years, as well as the effects of TCM monomers, effective components and TCM compounds on the permeability of the BBB were summarized, so as to provide important guidance and direction for the future treatment of intracranial diseases by traditional Chinese and western medicine.

Effect of Traditional Chinese Medicine on Hepatic Disease by Inhibiting TLR4 Signaling Pathway / 中国实验方剂学杂志

Liver disease is the general term for all diseases that occur in the liver. In recent years, traditional Chinese medicine has certain advantages in the treatment of liver diseases. With a high experimental study value, good clinical efficacy and less adverse reactions, it has broad prospects. Toll-like receptor 4 (TLR4) signaling pathway is closely related to liver diseases. Its mechanism is to activate nuclear factor-κB (NF-κB) through tlr4-mediated signaling pathway, inhibit the secretion of such inflammatory factors as interleukin-1(IL-1), interleukin-6(IL-6) and tumor necrosis factor-alpha (TNF-α), and the inflammatory damage of liver cells, so as to further inhibit the effect of IL-1,IL-6, TNF-α in activating Hepatic Stellate Cell(HSC). The ways of blocking TRL4 pathway are as follows:Inhibiting the expression of TLR4,Inhibiting the dimerization of TLR4. Blocking intracellular signal transduction:①acting on the binding protein; ②acting on the kinase IRAKs; ③acting on TLRAFst. In these ways, the TRL4 pathway is blocked, the inflammation is inhibited, and the anti-liver disease effect is achieved. Therefore, inhibiting or enhancing TLR4 signaling pathway or intervening in some links of TLR4 signaling pathway has become a new strategy for the treatment of liver diseases. Toll-like receptor 4 signaling pathway has become one of the targets of traditional Chinese medicine (TCM) against liver diseases. In this paper, the recent literatures on the effect of TCM in resisting activation of TLR4 signaling pathway and the effect of anti-liver diseases through monomers and effective parts of TCM, extracts of TCM and compound prescriptions of TCM were collected and summarized to provide important guiding significance and direction for the treatment of liver diseases by TCM and WM in the next step.