ABSTRACT
ObjectiveTo summarize the history and modern clinical application of Renshen Baidusan. MethodThe bibliometric method was used to retrieve the relevant publications of Renshen Baidusan from the ancient book database and China National Knowledge Infrastructure （CNKI）. The publications were screened according to the inclusion and exclusion criteria. The information of dynasty， book title， function， dosage and so on was extracted， on the basis of which the history， composition， dosage， decocting method， original medicinal plants， processing， and modern clinical application of this prescription were analyzed. ResultRenshen Baidusan was first recorded in the Formulary of the Bureau of Taiping People's Welfare Pharmacy， consisting of Bupleuri Radix， Glycyrrhizae Radix et Rhizoma， Platycodonis Radix， Ginseng Radix et Rhizoma， Chuanxiong Rhizoma， Poria， Aurantii Fructus， Peucedani Radix， Notopterygii Rhizoma et Radix， Angelicae Pubescentis Radix， Zingiberis Rhizoma Recens， and Menthae Haplocalycis Herba and with the effect of dispersing cold， removing dampness， reinforcing Qi， and relieving exterior. Later generations of physicians used this prescription on the basis of the record in Formulary of the Bureau of Taiping People's Welfare Pharmacy to treat cold （frequency of 112， 22.63%） and seasonal cold （frequency of 83， 16.77%）. Renshen Baidusan is widely used in modern clinical practice to treat respiratory diseases （frequency of 42， 17.65%）， skin diseases （frequency of 34， 14.29%）， and infectious diseases （frequency of 33， 13.87%）. This prescription is often modified to treat the syndrome of internal deficiency and external contraction， or external contraction of wind， cold and damp pathogens without deficiency of healthy Qi， which fully embodies the concept of treating different diseases with the same method in traditional Chinese medicine. ConclusionThe textual research reveals the key information of the classical prescription Renshen Baidusan， providing a basis for the subsequent development and application of compound preparations.
ABSTRACT
ObjectiveTo study the mechanism of Renshen Baidusan in regulating adenylate-activated protein kinase （AMPK）/Unc-51-like kinase 1 （ULK1） autophagy pathway to inhibit mucosal barrier damage in the mouse model of ulcerative colitis （UC）. MethodSixty SD rats were randomized into normal， model， sulfasalazine enteric-coated tablets （0.312 5 g·kg-1， western medicine）， and high-， medium-， and low-dose （31.2， 15.6， 7.8 g·kg-1， respectively） Renshen Baidusan groups. The UC model was induced by 2，4，6-trinitrobenzenesulfonic acid （TNBS）/50% ethanol. The drugs were administrated by gavage for 2 weeks， and then the histopathological changes of the colon were examined. Real-time quantitative polymerase chain reaction was conducted to measure the mRNA level of AMP-activated protein kinase subunit alpha （AMPKα）. Western blot was employed to determine the protein levels of closure protein （Occludin）， compact linking protein-2 （Claudin-2）， autophagy marker p62， microtubule-associated protein 1 light chain 3B （LC3B）， phosphorylated AMPK （p-AMPK）， and phosphorylated ULK1 （p-ULK1）. ResultCompared with the normal group， the model group showed increased colon injury score （P<0.05）， down-regulated mRNA level of AMPKα （P<0.05） and protein levels of p-AMPK， p-ULK1， and Occludin， decreased LC3Ⅱ/Ⅰ ratio （P<0.05）， and up-regulated protein levels of p62 and Claudin-2 （P<0.05）. Compared with the model group， all the doses of Renshen Baidusan lowered the colon injury score， up-regulated the mRNA level of AMPKα and the protein levels of p-AMPK， p-ULK1， and Occluding， increased LC3Ⅱ/Ⅰ ratio， and down-regulated the protein levels of p62 and Claudin-2. Moreover， the medium-dose group showed a significant intervention effect （P<0.05）. ConclusionRenshen Baidusan can protect the intestinal mucosal barrier from damage， and the medium dose showed the best efficacy. It may activate the AMPK/ULK1 pathway to accelerate the transformation of LC3Ⅰ to LC3Ⅱ and promote the degradation of p62， so as to improve the function of Occludin and Claudin-2 and repair the mechanical damage of the intestinal barrier.
ABSTRACT
ObjectiveTo explore the mechanisms of internal treatment （Renshen Baidusan）， external treatment （Yurui Enema）， and combination of the two methods in treating intestinal mucosal injury in the rat model of ulcerative colitis （UC） from the changes of phosphatidylinositol-3 kinase （PI3K）/protein kinase B （Akt）/nuclear factor-κB （NF-κB） pathway. MethodFifty SPF-grade SD rats were randomized into blank， model， Renshen Baidusan （15.6 g·kg-1）， Yurui Enema （25 g·kg-1）， and combined treatment （15.6 g·kg-1 Renshen Baidusan + 25 g·kg-1 Yurui Enema） groups （n=10）. The rat model of UC was established in other groups except the blank group by 2，4， 6-trinitrosulfonic acid （TNBS）/ethanol. The rats were administered with corresponding drugs once a day for 14 consecutive days since the 8th day after modeling. The histopathological changes of colon were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor （TNF）-α， interferon （IFN）-γ， interleukin （IL）-4， and IL-10 in the colon tissue. The apoptosis of colon epithelial cells was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The location and expression of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， TNF-α， and IL-6 in the colon tissue were examined by immunohistochemistry. Real-time quantitative fluorescence polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of the proteins in the PI3K/Akt/NF-κB pathway in the colon tissue. ResultIn the model group， HE staining showed a large number of inflammatory cell infiltration in the mucosa and submucosa. Compared with the blank group， the model group showed elevated levels of TNF-α and IFN-γ and lowered levels of IL-4 and IL-10 in the colon tissue， increased apoptosis rate of colon epithelial cells， increased positive expression of Bax， TNF-α， and IL-6， and decreased positive expression of Bcl-2 （P<0.05）. Moreover， the model group showed up-regulated mRNA levels of PI3K， Akt， and NF-κB and protein levels of PI3K， p-PI3K， Akt， p-Akt， p65， p-p65， Bax， and cleaved Caspase-3， increased Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratios， and down-regulated protein levels of NF-κB suppressor protein α（IκBα）， Bcl-2， and Caspase-3 in the colon tissue （P<0.05）. Compared with the model group， the internal treatment， the external treatment， and the combination （referred to as the three groups） alleviated the colonic mucosal injury， lowered the levels of TNF-α and IFN-γ and elevated the levels of IL-4 and IL-10 in the colon tissue， decreased the apoptosis rate of colon cells， inhibited the positive expression of Bax， TNF-α， and IL-6， and promoted the positive expression of Bcl-2 （P<0.05）. Furthermore， the combination group down-regulated the mRNA level of PI3K （P<0.05）. The three groups down-regulated the mRNA levels of Akt and NF-κB and the protein levels of p-PI3K， Akt， p-Akt， p65， p-p65， Bax， and cleaved Caspase-3 in the colon tissue， decreased the Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratios， and up-regulated the protein levels of IκBα， Bcl-2， and Caspase-3 （P<0.05）. ConclusionRenshen Baidusan， Yurui Enema， and their combination may inhibit the activation of PI3K/Akt/NF-κB signaling pathway and regulate the expression of genes and proteins related to this pathway to achieve anti-inflammatory and anti-apoptotic effects， thus restoring the intestinal mucosal barrier function of UC rats.
ABSTRACT
ObjectiveTo explore the mechanism of Renshen Baidusan in repairing intestinal mucosa in ulcerative colitis （UC） by regulating autophagy to scavenge peroxides. MethodThe mouse model of UC was induced by free drinking of 3.0% dextran sulphate sodium （DSS） solution. Sixty male C57BL/6J mice were randomized into normal， model， mesalazine （0.3 g·kg-1）， and high-， medium-， and low-dose （12.35， 8.22， 4.11 g·kg-1， respectively） Renshen Baidusan groups （n=10）. The mice were administrated with corresponding drugs by gavage for 7 consecutive days. The colon tissue was stained with hematoxylin-eosin （HE） to reveal the pathological changes， and Alcian blue-Periodic acid Scheff （PAS/AB） staining was employed to observe the goblet cell changes. The fluorescence expression of reactive oxygen species （ROS） in the colon tissue was detected by the immunofluorescence assay. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were measured by the biochemical methods. Western blot was employed to determine the expression levels of proliferating cell nuclear antigen （PCNA）， microtubule-associated protein 1 light chain 3 （LC3）， leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5）， and p62. ResultDestroyed mucosal epithelial structure， intestinal gland destruction， loss of goblet cells， and massive infiltration of inflammatory cells appeared in the model group. Compared with the normal group， the model group showed increased tissue damage injury （TDI） score of the colon tissue， decreased SOD activity and LC3Ⅱ/Ⅰ， PCNA value， and elevated levels of p62， MDA， ROS， and LGR5 （P<0.05）. Compared with the model group， different doses of Renshen Baidusan decreased the TDI score， promoted the generation of new goblet cells， elevated the levels of PCNA， LGR5， SOD， and LC3Ⅱ/Ⅰ， and lowered the levels of p62， MDA， and ROS （P<0.05）. Moreover， the low dose group showed the best performance （P<0.05）. ConclusionRenshen Baidusan can promote intestinal epithelial repair by activating intestinal autophagy， alleviating oxidative stress， and promoting intestinal stem cell proliferation and differentiation.
ABSTRACT
To explore the clinical value of repairing massive soft tissue defects of shank and foot with diverse combined flaps with the help of 3D-CTA technique. Methods From March, 2011 to May, 2018, 7 pa-tients with massive soft tissue defects (defect area:21 cm×14 cm-53 cm×16 cm) of shank and foot were treated with combined flaps, including free anterolateral thigh flaps(ALTP) combined with local transferred sural neurocuta-neous vascular flaps in 2 cases, free ALTP combined with local transferred supracondylar flap in 2 cases, free thora-co-umbilical flaps plus local transferred gastrocnemius muscular flaps in 1 case, and free ALTP plus free thoraco-um-bilical flap in 1 case.Free ALTP and free thoraco-umbilical flap respectively combined with double bridge flaps using the both ends of posterior tibial vessel from the healthy limb to form vascular pedicles in 1 case. All cases received 3D-CTA to observe the distribution and anastomosis of perforator vessel. Regular followed-up was made post-opera-tively. Results All patients had been followed-up for 6-18 months. Outpatient service combined with telephone follow-up was adopted. All flaps survived, and flap shape, colour and lustre, elasticity got good recover. At the last follow-up, thermann scale function assessment: 4 cases were excellent, 2 were good, and 1 was fair. Conclusion It is a feasible and effective method to repair massive soft tissue defects of shank and foot using differently combined flaps. Although the surgery can be risky, the method can effectively reduce the rate of limb disability, restore the limb func-tion and shorten the course of treatment.Preoperative 3D-CTA can get the vessel anatomical structure and diameter at donor and recipient sites, which will guide the operation program design and implementation so as to shorten the oper-ation time and improve the accuracy rate of vascular anastomosis.
ABSTRACT
s: The onset of Crohn’s disease (CD) is the interaction of environment, heredity, infection, immune and other factors. It is also closely related to abnormal immune functions. Without special treatment, CD is identified as a modern refractory disease. By syndrome differentiation and treatment, traditional Chinese medicine (TCM) can effectively relieve disease conditions, improve the quality of life and reduce side effects of modern medication. The core compatibility ofBai-Zhu andFu-Ling can reinforce spleen-qi and dispel dampness, which met the common pathogenesis of CD. Therefore, the combination is comprehensively used in the compound prescription. Our previous study found thatBai-Zhu Fu-Ling decoctioncan reduce the vasoactive intestinal peptide (VIP) of animal model of spleen-qi deficiency, downregulate VIP receptors, decrease the affinity of VIP receptors and improve animal model’s sIgA. To further clarify the effects about neurotransmitters and their correlation with the immune system in the pathogenesis of CD and the intervention mechanism treated by different proportional compatibility ofBai-Zhu Fu-Ling decoction, we studied influences of the decoction on related transmitters of nerve- immune network and functions of receptors, as well as cytokine secretion and signal transduction of TLR4-NF-κB. Our studies can provide references and foundations to further explore TCM treatment of CD.
ABSTRACT
This study was aimed to observe the effect of Bai-Zhu Fu-Ling (BZFL) Decoction in different proportion-ing on VIP and VIPR1 in Crohn's disease (CD) rats with spleen deficiency syndrome, in order to further explore the immunologic mechanism of BZFL Decoction on CD. The CD rat model with spleen deficiency syndrome was estab-lished using exhaustion and hunger. The model rats were treated by BZFL Decoction with different proportioning, and immunohistochemistry (IHC) was used to detect the expression of VIP and its receptor in colon tissues. The results showed that comparing to the blank control group, the level of VIP and its receptor of the model group significantly increased (P< 0.05). Comparing to the model group, the level of VIP and its receptor in BZFL Decoction B5 group (Rhizoma A tractylodis Macrocephalae:Poria = 12:15), B6 group (Rhizoma A tractylodis Macrocephalae:Poria = 15:12) and B7 group (Rhizoma A tractylodis Macrocephalae:Poria = 18:9) was significantly decreased (P< 0.05). It was con-cluded that the effect of BZFL Decoction of B5 group, B6 group and B7 group was better than other groups in VIP and its receptor which can regulate the VIP and its receptor, inhibit the releasing of inflammatory factors and reduce intestinal inflammation injury.
ABSTRACT
Objective:To study the effects of compatibility circumstances on guizhi's effect in dispelling cold and relieving exterior in complex prescriptions. Methods:202 formulae that effected on Sanhanjiebiao were collected from 1425 formulae with guizhi,and the frequency of herbs combining with guizhi in 202 formulae was ranked from high to low. Results:According to the compatibility frequency from high to low,herbs are:Radix Ledebouriellae(60.89%) ,Herba Ephedrae(36.63%) ,Notopterygium Incisum Ting ex H.T.Chang(27.23%) ,Radix Angelicae Dahuricae(14.85%) ,Rhizoma Zingiberis Recens(11.39%) ,Herba Schizonepetae(5.94%) ,Radix Ledebouriellae and Herba Schizonepetae(4.46%) successively. Conclusion:It showed that guizhi should combine with corresponding herbs to form compatibility circumstances to exert the effect of Sanhanjiebiao in formula,and the function exertion will be effective.