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The high disability, mortality and morbidity of diabetic ulcers make it urgent to explore effective strategies for diabetic wound repair. TrxR1 plays a vital role in regulating redox homeostasis in various pathologies. In the present study, the effect of berberine (BBR) on diabetic wounds was investigated in streptozotocin (STZ)-induced diabetic rats and a high glucose (HG)-induced cell model, and the mechanism of BBR on TrxR1 was elucidated. BBR treatment remarkably accelerated wound healing and enhanced extracellular matrix (ECM) synthesis and significantly inhibited HG-induced HaCaT cell damage. Further analysis indicated that BBR activated TrxR1, suppressed its downstream JNK signaling, thereby inhibiting oxidative stress and apoptosis, promoted cell proliferation, down-regulated matrix metalloproteinase (MMP) 9 (MMP9) and up-regulated transforming growth factor-β1 (TGF-β1) and tissue inhibitors of MMP 1 (TIMP1), resulting in accelerated wound healing. Importantly, the enhancement of BBR on wound repair was further abolished by TrxR1 inhibitor. Moreover, in diabetic wounds induced by a combination of STZ injection and high-fat diet, BBR significantly increased wound closure rate and TrxR1 expression, and this was reversed by TrxR1 inhibitor. These data indicated that topical BBR treatment accelerated diabetic wound healing by activating TrxR1. Targeting TrxR1 may be a novel, effective strategy for restoring redox homeostasis and promoting diabetic wound healing.

As a complex and challenging complication for the patients with diabetes mellitus, diabetic ulcers are difficult to heal and current strategies cannot fulfill the patients' requirements. Pien Tze Huang (PZH) is a standardized medicine approved for various wounds treatments, and this study systematically investigated the effect and mechanism of intragastric administration of PZH (I-PZH) on diabetic wound healing.The effect of I-PZH on the healing of full-thickness wounds in rats with diabetes mellitus which was induced by high fat diet followed by streptozotocin injection was evaluated, and RNA sequencing (RNA-seq) and targeted central carbon metabolism metabolomics were combined to explore the underlying mechanism. I-PZH promoted wound healing, facilitated extracellular matrix synthesis, and maintained body weight of rats, but did not affect fasting blood glucose levels. Additionally, I-PZH significantly decreased 8-OHdG, cleaved caspase 3 and MMP9 levels, and increased TGF-β1 expression. RNA-seq analysis showed that I-PZH inhibited inflammation and that the vital common targets were TLR2, IL-17A and IL-1β; specifically affected "energy derivation by oxidation of organic compounds" with UQCRC1, NDUFS3 and SDHA as vital specific targets. Further experiments confirmed that I-PZH reduced TLR2, IL-17A and IL-1β, increased UQCRC1, SDHA, NDUFS3, promoted ATP synthesis and restored activity of mitochondrial respiratory chain complexes I and III in diabetic wounds. Metabolomics by HPLC-MS/MS analysis showed that I-PZH reversed multiple energy metabolism-related metabolites such as glucuronic acid, GMP, d-gluconic acid, cis-aconitic acid, ribose 5-phosphate and pantothenate.This study highlights the important role of inflammation and energy generation in diabetic wound healing, reveals wound repair mechanism of PZH and promotes its clinical application in diabetic wound treatment.

Diabetic ulcers bring about high morbidity and mortality in patients and cause a great economic burden to society as a whole. Since existing treatments cannot fulfil patient requirements, it is urgent to find effective therapies. In this study, the wound healing effect of topical notoginsenoside R1 (NR1) treatment on diabetic full-thickness wounds in type II diabetes mellitus (T2DM) was induced by the combination of a high-fat diet and streptozotocin (STZ) injection. NR1 significantly increased the wound closure rate, enhanced extracellular matrix (ECM) secretion, promoted collagen growth, increased platelet endothelial cell adhesion molecule-1 (CD31) expression, and decreased cleaved caspase-3 expression. RNA-Seq analysis identified ECM remodeling and inflammation as critical biological processes and Timp1 and Mmp3 as important targets in NR1-mediated wound healing. Further experiments showed that NR1-treated wounds demonstrated higher expression of tissue inhibitor of metalloproteinase 1 (TIMP1) and transforming growth factor-β1 (TGFβ1) and lower expression of matrix metallopeptidase 9 (MMP9), matrix metallopeptidase 3 (MMP3), interleukin-1β (IL-1β), and interleukin-6 (IL-6) than diabetic wounds. These investigations promote the understanding of the mechanism of NR1-mediated diabetic wound healing and provide a promising therapeutic drug to enhance diabetic wound healing.

Background Magnolia bark (Magnolia Officinalis REHD. & WILS. and Magnolia officinalis REHD. & WILS. VAR. biloba REHD. & WILS, Hou Po in Chinese), is widely applied in clinical prescriptions and Chinese patent medicines. Origin place is a crucial factor affecting the quality of Hou Po, and chemical composition is an important index for evaluating its quality, which is closely related to its clinical efficacy. This study aims to develop a novel method for rapidly, accurately and comprehensively identifying the origin places of Hou Po and predicting the contents of its important chemical components. Methods High performance liquid chromatography was used to analyze the contents of magnolol and honokiol and ultra-performance liquid chromatography the contents of magnocurarine and magnoflorine. The cold soak method was used to determine the contents of water-soluble extracts. The E-nose and colorimeter were used to determine the odor and color characteristics, respectively, of the collected Hou Po samples. Results Using several statistical algorithms, different discriminant models based on the E-nose and colorimeter data were established to distinguish the origin place of Hou-Po and predict the chemical components of honokiol, magnolol, magnocurarine, magnoflorine and water-soluble extracts. The results showed that the Random Forest classifier combined with the ten-fold cross-validation method provided the highest classification accuracy for origin place, accounting for 99.53% among these models. The correlation coefficients between predicted and experimental values of the five chemical components were all higher than 0.96. Conclusion This study has indicated that the electronic nose and colorimeter are promising methods for evaluating the quality of Chinese herbal medicines both qualitatively and quantitatively.

Background and purpose Transcription factors (TFs) play a critical role in the cerebral ischemia/reperfusion injury (IRI). Panax notoginseng saponins (PNS) are extensively used in the treatment of acute cerebral ischemia in China, but the mechanism of their effects, especially at the TF level, remains unclear. In this study, a combination of transcriptomics, proteomics and network pharmacology analysis was used to identify the key TFs involved in the protection of PNS against middle cerebral artery occlusion (MCAO)-induced IRI. Methods and results Sprague-Dawley rats which were subjected to 1.5 hours of MCAO-induced occlusionand then followed by reperfusion, were treated with PNS at a concentration of 36 mg/kg or 72 mg/kg daily for 7 days. PNS significantly decreased neurological deficient scores and infarction rate; prevented cerebral tissue damage; and reduced CASP3 activity, levels of TNF, IL1B and CCL2 after IRI. Through a combination of transcriptomics and proteomics, 9 critical TFs were identified, including Excision repair cross-complementing group 2 (ERCC2), Nuclear receptor subfamily 4 group A member 3 (NR4A3) and 7 other TFs. The targets of ERCC2 and NR4A3, such as Ubxn11, Ush2a, Numr2, Oxt, Ubxn11, Scrt2, Ttc34 and Lrrc23, were verified by using real-time PCR analysis. RNA-seq analyses indicated that PNS regulated nerve system development and inflammation, and the majority of the identified TFs were also involved in these processes. By using network pharmacology analysis, 73 chemical components in PNS were predicted to affect ERCC2, NR4A3 and 3 other identified TFs. Conclusion ERCC2, NR4A3 and 7 other TFs were of importance in the protection of PNS against IRI. This study promoted the understanding of protective mechanism of PNS against cerebral IRI and facilitated the identification of possible targets of PNS.

In recent years, the domestic and international trade volumes of Chinese medicinal materials (CMMs) keep increasing. By the end of 2019, the total amount of exported CMMs reached as high as US $1.137 billion, while imported was US $2.155 billion. A stable and controllable quality system of CMMs apparently becomes the most important issue, which needs multifaceted collaboration from harvesting CMMs at a proper season to storing CMMs at a proper temperature. However, due to imperfect storage conditions, different kinds of deteriorations are prone to occur, for instance, get moldy or rancid, which not only causes a huge waste of CMM resources but also poses a great threat to clinical medication safety and public health. The key issue is to quickly and accurately distinguish deteriorated CMM samples so as to avoid consuming low-quality or even harmful CMMs. However, some attention has been paid to study the changing quality of deteriorated CMMs and a suitable method for identifying them. In this study, as a medicine and food material which easily becomes rancid, armeniacae semen amarum (ASA) was chosen as a research objective, and experimental ASA samples of different rancidness degrees were collected. Then, various kinds of analytical methods and technologies were applied to explore the changing rules of ASA quality and figure out the key indicators for the quality evaluation of ASA in the rancid process, including the human panel, colorimeter, electronic nose, and GC/MS. This study aims to analyze the correlation between the external morphological features and the inner chemical compounds, to find out the specific components from “quantitative change” to “qualitative change” in the process of “getting rancid,” and to discover the dynamic changes in the aforementioned key indicators at different stages of rancidness. The results showed since ASA samples began to get rancid with the extension of storage time, morphological features, namely, surface color and smell, changed significantly, and the degree of rancidness further deepened at the same time. Based on macroscopic identification accomplished via the human panel, ASA samples with varying degrees of rancidness were divided into four groups. The result of colorimeter analysis was in agreement with that of the human panel, as well as the determination of the amygdalin content and peroxide value. Moreover, there were obvious differences in the amygdalin content and peroxide value among ASA samples with different rancidness degrees. With a higher degree of rancidness, the content of amygdalin decreased, while the peroxide value increased significantly. The rancidness degree of ASA has a negative correlation with the amygdalin content and a positive correlation with the peroxide value. The newly discovered nonanal and 2-bromopropiophenone in rancid ASA samples may be the key components of “rancidity smell,” and these two components would be the exclusive components that trigger “quantitative change” to “qualitative change” in the process of rancidness of ASA. This study sheds light on studying the internal mechanism of “rancidness” of CMMs and provides an important basis for the effective storage and safe medication of easy-to-get rancid herbs, and it also plays an important foundation for the establishment of a stable and controllable quality system for CMMs.

Background Amomi fructus is a famous traditional Chinese medicine (TCM) that can exert beneficial effects during the treatment of gastrointestinal diseases and is used widely in China and other countries in Southeast Asia. However, the nonvolatile active ingredients that are present in the water extractions from A. fructus used to treat gastrointestinal diseases have yet to be elucidated. The goal of this study was to identify the nonvolatile active ingredients of A. fructus. Methods We used an in situ single-pass intestinal perfusion (SPIP) model to identify the active ingredients of A. fructus that play significant roles in gastrointestinal absorption. In addition, we developed a high-performance liquid chromatography (HPLC) method to identify key fractions in intestinal outflow perfusate. Results Nineteen components were identified in a water extraction from A. fructus; these exhibited different absorption capabilities in different intestinal segments. Of these, six components were determined by the newly developed HPLC method: catechin, vanillic acid, epicatechin, polydatin, isoquercitrin, and quercitrin. Conclusions The current study aimed to identify the active ingredients present in water extractions prepared from A. fructus in a single-intestinal perfusate from rats. Our findings provide an experimental basis to explain the pharmacodynamic actions of A. fructus.