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Danggui Buxuetang， derived from Clarifying Doubts about Damage from Internal and External Causes （Volume 2）： Treatise on Heat Injury to Stomach Qi（《内外伤辨惑论卷中·暑伤胃气论》） by LI Dongyuan in the Jin and Yuan dynasties， is a classic and famous formula for tonifying qi and generating blood that has been inherited and promoted by successive generations of medical practitioners and has been included in the "Catalogue of Ancient Classical Prescriptions （First Batch）" published by the National Administration of Traditional Chinese Medicine in 2018. The paper analyzed the historical origin， composition， dosage， processing， preparation， decocting， and taking methods， efficacy， and application of the classic formula Danggui Buxuetang by consulting ancient and modern literature and combining the key information examination principles of ancient classic prescriptions. A total of 604 pieces of information on relevant ancient literature were collected， including 186 ancient Chinese medical books， of which 40 （five in the Jin and Yuan dynasties， 19 in the Ming Dynasty， and 16 in the Qing Dynasty） had detailed records of composition， processing， and dosage. Danggui Buxuetang is mainly comprised of Astragali Radix and Angelicae Sinensis Radix. According to the ancient and modern dose conversion， there are 37.3-38.1 g of Astragali Radix and 7.5-7.6 g of Angelicae Sinensis Radix in the formula. Astragali Radix is preferably fried with honey and Angelicae Sinensis Radix with wine. Astragali Radix and Angelicae Sinensis Radix are decocted with 600 mL of water to 300 mL， and taken warm before meals. The main effect of this formula are described in ancient books as blood deficiency and fever， with symptoms of muscle fever， dryness and heat， irritability and thirst， red eyes and face， sleeplessness in daytime and night， and surging and feeble pulse which is weak under hard pressing， and it is a famous formula for replenishing qi and generating blood. Modern research shows that Danggui Buxuetang is commonly used in the treatment of various kinds of anemia， diabetic nephropathy， tumors， and cardiovascular and cerebrovascular diseases. The above research results can provide a reference for the subsequent development and research on the classic formula Danggui Buxuetang.
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The occurrence and development of malignant tumors seriously affect the survival time and quality of life of people all over the world， and finding proper treatment methods has been a focus for doctors. Especially in recent years， traditional Chinese medicine （TCM） has developed and attracted the attention of doctors and patients. From the perspective of TCM syndrome differentiation and treatment， deficiency and stasis are the most fundamental causes of malignant tumors， and supplementing deficiency and removing stasis can be regarded as the basic criteria of TCM treatment of malignant tumors. TCM prescriptions can treat diseases by means of multiple components and multiple targets， with the characteristics of slight side effect and high efficacy， safety and cost performance， as well as easiness to be accepted and taken. As a classic recipe for invigorating Qi and generating blood， Danggui Buxuetang consists of Astragali Radix -Angelicae Sinensis Radix 5∶1. It has excellent effects in anti-tumor， bone marrow suppression after chemotherapy， immune function decline， anemia， heart and cerebral vessels protection， blood deficiency-led fever， diabetes， anti-atherosclerosis， anti-fatigue， anti-radiation， myocardial ischemia alleviation， inhibition of platelet aggregation， liver damage， etc. In addition， with many active anti-tumor ingredients， Danggui Buxuetang can exert anti-tumor effects via acting on multiple targets in different binding sites. However， there has been a lack of reviews on the role of Danggui Buxuetang in malignant tumors so far. Therefore， in this paper， the functions of Danggui Buxuetang in malignant tumors were reviewed. Besides， molecular docking technology was used to analyze the main active anti-tumor ingredients and action targets of Danggui Buxuetang.
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ObjectiveTo investigate the intervention effect of Danggui Buxuetang on oxidative stress and inflammatory response in diabetic kidney disease （DKD） rats from its improvement of podocyte mitochondrial dysfunction. MethodSD rats were randomly divided into the control group and modeling group， and the ones in the latter group rats were fed a high-glucose and high-fat diet and then intraperitoneally injected with a small dose of streptozotocin （STZ） for inducing type 2 diabetes. The successfully modeled rats were randomized into the model group， high- and low-dose （1.44 and 0.72 g·kg-1） Danggui Buxuetang groups， and irbesartan （0.017 g·kg-1）group and gavaged with the corresponding drugs， while those in the normal and model groups with an equal volume of normal saline. After 20 weeks of drug intervention， the urinary microalbumin-to-urine creatinine ratio （UACR） and serum malondialdehyde （MDA） content and manganese superoxide dismutase （MnSOD） activity in each group were measured. The pathological changes in renal tissue were observed by Masson trichrome staining， and periodic acid-silver metheramine （PASM） staining， followed by the observation of ultrastructural changes in podocytes under the transmission electron microscope （TEM）. The expression level of reactive oxygen species （ROS） in rat kidney tissue was detected using a fluorescent probe dihydroethidium （DHE）. The protein expression levels of peroxisome proliferator-activated receptor γ -coactivator -1α （PGC-1α）， nucleotide-binding domain like receptor protein 3 （NLRP3）， and Wilms tumor protein-1 （WT-1） were measured by immunohistochemistry （IHC）， and the expression levels of NLRP3， interleukin-1β （IL-1β），and WT-1 in podocytes by immunofluorescence （IF） assay. The mRNA expression levels of PGC-1α and NLRP3 in the renal tissues were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expression levels of PGC-1α， MnSOD， NLRP3， and IL-1β were assayed by Western blot. ResultCompared with the normal group， the model group exhibited elevated UACR and MDA content， weakened MnSOD activity （P<0.01）， glomerular hypertrophy， thickened basement membrane， mesangial hyperplasia， increased extracellular matrix， K-W nodules， podocyte mitochondrial swelling， disordered mitochondrial cristae， foot process fusion or loss， vacuolization， increased ROS （P<0.01）， enhanced NLRP3 and IL-1β but diminished WT-1 expression in podocytes， down-regulated PGC-1α mRNA expression （P<0.01） and PGC-1α and MnSOD protein expression （P<0.01）， and up-regulated NLRP3 mRNA expression and NLRP3 and IL-1β protein expression （P<0.01）. Compared with the model group， Danggui Buxuetang high-dose group significantly decreased UACR and MDA， enhanced MnSOD activity （P<0.05， P<0.01）， improved renal histopathology and podocyte mitochondrial ultrastructure， decreased ROS （P<0.05， P<0.01） and NLRP3 and IL-1β expression in podocytes， enhanced WT-1 expression in podocytes， up-regulated the mRNA and protein levels of PGC-1α and MnSOD， and down-regulated the mRNA and protein levels of NLRP3 and IL-1β （P<0.05， P<0.01）. ConclusionDanggui Buxuetang alleviates oxidative stress， reduces inflammatory response， protects kidney， and delays the progression of DKD possibly by improving the mitochondrial dysfunction in podocytes of DKD rats.
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ObjectiveTo investigate the intestinal absorption characteristics of multi-index components in Danggui Buxuetang with drug absorption simulating system （DASS） established by everted intestinal sac model. MethodThe intestinal absorption solution at different time points after administration of Danggui Buxuetang was collected and detected by high performance liquid chromatography （HPLC）， acetonitrile （A）-0.2% glacial acetic acid solution （B） was used as the mobile phase for gradient elution （0-16 min， 15%-23%A； 16-20 min， 23%-28%A； 20-25 min， 28%-30%A； 25-30 min， 30%A； 30-35 min， 30%-65%A； 35-45 min， 65%-95%A）， the detection wavelength was 302 nm. HPLC fingerprint of intestinal absorption solution was established and the common peak was calibrated， and the relative cumulative absorption rate of each index component was calculated. The relative cumulative absorption curves of components were fitted with various mathematical models by DDSolver 1.0 to explore the absorption law of different components. ResultThe absorption process of C2 （calycosin-7-glucoside） and C6 in Danggui Buxuetang was in line with zero-order equation， C9 was best fitted by Weibull equation， and the remaining 7 components were in line with Makoid-Banakar equation. C1 with C2， C3， C5， C7 and C10， C2 with C5 and C7， C3 with C4， C5， C7 and C10， C4 with C6 and C10， C5 with C7， C6 with C10， C7 with C10， C8 with C9 were absorbed simultaneously during the absorption process. With the prolongation of time， the overall cumulative absorption rate of Danggui Buxuetang increased. At 120 min， the overall cumulative absorption rate of Danggui Buxuetang exceeded 38%， and reached 49.14% at 180 min. ConclusionTen ingredients in Danggui Buxuetang are absorbed in the jejunum， but absorption law of various components is different， which shows that the intestinal absorption of compound preparations of traditional Chinese medicine （TCM） has multiple characteristics. Intestinal absorption study of TCM compound preparations with chemical composition as the index can reveal some of its absorption law， but it is not complete.
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Astragali Radix-Angelicae Sinensis Radix （AA） is a basic pair of drugs mainly targeting the syndrome characteristics of Qi and blood diseases. LI Dong-yuan's Danggui Buxuetang （DBT） is composed of AA， which is mainly used to tonify Qi and generate blood， with main indications of Qi deficiency and blood deficiency， blood heat and so on. It is favored by doctors because of its refined prescription and remarkable curative effect. However， there are many compatibility ratios of AA in different prescriptions in ancient books， and their efficacy and indications are also slightly different. This research showed that DBT also had the effect of invigorating Qi and activating blood， and the previous study of the group showed that 3∶1 compatibility ratio of the two herbs in the total amount of 36 g had more obvious effect of invigorating Qi and activating blood. By consulting the relevant literature， it was found that the drug pair had a certain effect of invigorating Qi and activating blood in various compatibility ratios such as 1∶1， 3∶1， 1∶5， 3∶2， 2∶1， 5∶1. The corresponding pharmacological effect mainly included regulating the energy metabolism of substances， regulating immune function， reducing blood viscosity， anti-oxidation stress， anti-inflammation， lowering blood lipids， lowering blood sugar， protecting heart function， protecting blood vessel wall， intervening angiogenesis， fighting against organ tissue fibrosis and so on. Regardless of the AA single-medicine's activating blood effect and the theory that "Qi circulation leads to blood circulation" or the drug pair's manifestation in modern pharmacological effects， all of these have confirmed that AA's effect of invigorating Qi and activating blood does exist， and the difference of action performance caused by different ratios of AA is closely related to dosage and proportion， which needs further study. Based on the study focusing on the effect of tonifying Qi and generating blood， it is easy to ignore the effect of invigorating Qi and activating blood， which limits the clinical application of the latter. Therefore， the tonifying Qi and activating blood circulation effect of the drug pair is reviewed in this paper， so as to provide a theoretical basis for its clinical rational drug use and related research.