1.Preliminary Conception of Theory of Triple Energizer-nutrient-defense Loop
Yujing JIN ; Jianwen ZHAIWU ; Rui YANG ; Tong ZHANG ; Juhua PAN ; Shijing HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(18):213-224
The research on the essence of triple energizer has not reached a consensus. The correspondence between the existing understanding and the classical theory of triple energizer is still limited in terms of structure and function. According to the traditional theory, nutrient-defense takes channels as the main circulatory system, while the operation of nutrient-defense in the triple energizer remains unclear. Since little is known about the physical structure of the triple energizer, the role of triple energizer as a collection of other Zang-fu organs has been ignored in most cases. The new progress in anatomy paves the way for the research on the essence of triple energizer. The function and structure of triple energizer are similar to those of interstitium and interfacial fluid flow, which enriches our understanding of the macro and micro structures of triple energizer. The triple energizer is distributed throughout the body and composed of membrane and interstitial space. The material structure of triple energizer includes fiber scaffold, collagen fiber, mesenchymal stem cells, histiocytes, pericytes, and interstitial fluid. The functions of triple energizer include passing body fluids, operating nutrient-defense, distributing original Qi, and transmitting and changing pathogenic Qi. According to the available theories and research achievements, we put forward the concept of vertical and horizontal triple energizer, pointed out that triple energizer had independent structure and the features of Zang-fu organs, and preliminarily defined the spatial distribution of triple energizer. The relationship between channels and triple energizer is essential for discussing the operation of nutrient-defense. Telocyte (Tc) and telopod (Tp) has the characteristics of channels in function and structure. The connective tissue with the distribution of Tc and Tp belongs to the same material as the basic structure of interstitial/interfacial fluid flow system and the fibrous skeleton of interstitium. It is clear that channels and triple energizer have material commonality. From the operation paths of nutrient-defense, we proposed that channels may be soaked and attached in triple energizer and put forward the model of channels soaked and attached in triple energizer. By combining the circulation of nutrient-defense with the vertical and horizontal triple energize, we developed the theory of triple energizer-nutrient-defense loop to comprehensively describe the generation, transport, and metabolism of nutrient-defense in channels and triple energizer, aiming to provide a theoretical model for future studies of disease transmission and change from exterior to interior.
2.Huangjing Jiannao Granules Improve Learning and Memory Abilities and Cerebral Blood Flow in Rat Model of Vascular Cognitive Impairment via PI3K/Akt Signaling Pathway
Rui YANG ; Yumu TIAN ; Yujing JIN ; Jianwen ZHAIWU ; Tong ZHANG ; Zehua ZHAO ; Shijing HUANG ; Juhua PAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):52-60
ObjectiveTo study the effects of Huangjing Jiannao granules on learning and memory abilities and cerebral blood flow in the rat model of vascular cognitive impairment (VCI) and to explore the mechanism of Huangjing Jiannao granules in the treatment of VCI. MethodSeventy-two SPF-grade male SD rats were randomly selected, with 12 rats as the sham operation group. The remaining rats were subjected to bilateral carotid artery ligation (2-VO) for the modeling of VCI. According to the randomized block design, the successfully modeled rats were grouped as follows: model, donepezil hydrochloride (0.50 mg·kg-1), and low-, medium-, and high-dose (2.36, 4.72, 9.44 g·kg-1, respectively) Huangjing Jiannao granules. After 6 weeks of treatment, Morris water maze test and new object recognition test were conducted to evaluate the learning and memory abilities of the rats. After continuous gavage for 8 weeks, the cerebral blood flow was recorded by a laser microcirculation blood flow imager, and the survival and injury of hippocampal neurons were observed by Nissl staining. The expression of neuronal nuclear antigen (NeuN) in the hippocampus was detected by immunohistochemistry (IHC). The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum were determined by enzyme-linked immunosorbent assay. The protein levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), nuclear factor-κB p65 (NF-κB p65), and nuclear factor-κB inhibitor α (IκBα) in the hippocampus were determined by Western blot. ResultCompared with the sham operation group, the model group showed weakened learning and memory abilities (P<0.01), reduced blood flow in the whole brain, forebrain, and hindbrain (P<0.01), damaged neurons and reduced survived neurons in the hippocampal CA1 region (P<0.01), down-regulated expression of NeuN (P<0.01), elevated levels of IL-1β and TNF-α in the serum (P<0.01), up-regulated protein levels of PI3K, p-Akt, and NF-κB p65 in the hippocampal tissue, and down-regulated protein level of IκBα (P<0.01). Compared with the model group, medium- and high-dose Huangjing Jiannao granules improved the learning and memory abilities (P<0.05,P<0.01). High-dose Huangjing Jiannao granules increased the blood flow in the whole brain, forebrain, and hindbrain (P<0.05,P<0.01), and medium-dose Huangjing Jiannao granules increased the blood flow in the whole brain (P<0.05). All the doses of Huangjing Jiannao granules increased the number of survived neurons (P<0.05,P<0.01) and up-regulated the protein level of NeuN (P<0.05,P<0.01). Medium and high-dose Huangjing Jiannao granules lowered the level of TNF-α (P<0.05,P<0.01), down-regulated the protein levels of PI3K, p-Akt, and NF-κB p65 (P<0.05,P<0.01), and up-regulated the protein level of IκBα (P<0.01). ConclusionHuangjing Jiannao granules can improve the learning and memory abilities and promote the recovery of cerebral blood flow in the rat model of VCI induced by 2-VO by regulating the expression of proteins involved in the PI3K/Akt signaling pathway, inhibiting inflammation, and reducing hippocampal neuron injury.