Emodin (EMO) shows therapeutic promise for ulcerative colitis (UC), yet its clinical utility is hampered by low bioavailability. To rationally overcome this limitation, this study employed cocrystal engineering, strategically selecting tetramethylpyrazine (TMP)—a natural compound from traditional Chinese medicine—as the cocrystal coformer (CCF). The selection of TMP was guided by a systematic CCF screening strategy, incorporating extensive literature analysis of natural compound CCF candidates, computational chemistry methods to predict favorable hydrogen-bonding interactions and interaction sites with EMO, and machine learning assessment of cocrystallization propensity. Utilizing this rational design approach, we successfully synthesized and characterized a novel EMO-TMP cocrystal through comprehensive solid-state characterization techniques. The resulting cocrystal significantly enhanced the aqueous solubility of EMO while preserving its intrinsic bioactivity. Pharmacokinetic studies confirmed that the cocrystal formulation markedly improved the oral bioavailability of EMO. In a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) model, the EMO-TMP cocrystal demonstrated superior efficacy compared to EMO alone, effectively alleviating colitis symptoms and associated pathological markers. This enhanced in vivo efficacy is attributed to the significantly improved systemic exposure achieved through the rationally designed cocrystal. Our findings establish the EMO-TMP cocrystal as a highly promising strategy to surmount the physicochemical barriers of EMO, unlocking its full clinical potential for UC treatment. Critically, this work not only validates TMP as an efficient and safe CCF specifically suited for active pharmaceutical ingredients (APIs) rich in hydrogen-bond donors, but also exemplifies the value of leveraging formulation principles and compatible components inherent in traditional Chinese medicine through advanced crystal engineering approaches.

With various potential health-promoting bioactivities, genistein has great prospects in treatment of a series of complex diseases and metabolic syndromes such as cancer, diabetes, cardiovascular diseases, menopausal symptoms and so on. However, poor solubility and unsatisfactory bioavailability seriously limits its clinical application and market development. To optimize the solubility and bioavailability of genistein, the cocrystal of genistein and piperazine was prepared by grinding assisted with solvent based on the concept of cocrystal engineering. Using a series of analytical techniques including single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis, the cocrystal was characterized and confirmed. Then, structure analysis on the basis of theoretical calculation and a series of evaluation on the stability, dissolution and bioavailability were carried out. The results indicated that the cocrystal of genistein and piperazine improved the solubility and bioavailability of genistein. Compared with the previous studies on the cocrystal of genistein, this is a systematic and comprehensive investigation from the aspects of preparation, characterization, structural analysis, stability, solubility and bioavailability evaluation. As a simple, efficient and green approach, cocrystal engineering can pave a new path to optimize the pharmaceutical properties of natural products for successful drug formulation and delivery.

Co-crystal formation can improve the physicochemical properties of a compound, thus enhancing its druggability. Therefore, artificial intelligence-based co-crystal virtual screening in the early stage of drug development has attracted extensive attention from researchers. However, the complexity of developing and applying algorithms hinders it wide application. This study presents a data-driven co-crystal prediction method based on the XGBoost machine learning model of the scikit-learn package. The simplified molecular input line entry specification (SMILES) information of two compounds is simply inputted to determine whether a co-crystal can be formed. The data set includs the co-crystal records presented in the Cambridge Structural Database (CSD) and the records of no co-crystal formation from extant literature and experiments. RDKit molecular descriptors are adopted as the features of a compound in the data set. The developed model shows excellent performance in the proposed co-crystal training and validation sets with high accuracy, sensitivity, and F1 score. The prediction success rate of the model exceeds 90%. The model therefore provides a simple and feasible scheme for designing and screening co-crystal drugs efficiently and accurately.

目的 研究注射用丹参多酚酸(salvianolic acids for injection,SAFI)对氧糖剥夺后恢复(oxygen and glucose deprivation reperfusion,OGD/R)损伤PC12细胞的保护作用及机制.方法 采用网络药理学方法预测SAFI抗脑缺血再灌注损伤的作用靶点.建立OGD/R损伤PC12细胞模型,采用噻唑蓝(MTT)比色法和检测乳酸脱氢酶(LDH)的释放考察SAFI对PC12细胞活力的影响,吖啶橙/溴化乙锭(acridine orange/ethidium bromide,AO/EB)染色检测细胞凋亡,蛋白质印迹法(Western blot)检测B淋巴细胞瘤-2关联X蛋白(Bax)和B淋巴细胞瘤-2(Bcl-2)凋亡蛋白水平,进一步通过免疫荧光法研究SAFI保护OGD/R损伤PC12细胞的作用通路.结果 OGD/R损伤PC12细胞,导致细胞存活率明显降低,1和10 mg·mL-1的SAFI可以显著提高OGD/R后PC12细胞存活率,降低LDH释放.并且SAFI能够显著增加OGD/R损伤后抗凋亡蛋白Bcl-2的表达,抑制促凋亡蛋白Bax过表达.进一步研究表明,SAFI可以显著上调蛋白激酶B(protein kinase B,Akt)和信号转导及转录激活蛋白3(signal transducer and activator of transcription 3,STAT3)的磷酸化水平.结论 SAFI 能够抑制 OGD/R 对 PC12 细胞的损伤,是通过促进Bax和Bcl-2平衡的恢复,激活磷脂酰肌醇激酶(PI3K)/Akt和蛋白酪氨酸激酶2(janus kinase 2,JAK2)/STAT3信号通路实现的.

Salvianolic acid A (Sal A), a water-soluble ingredient in Danshen, has various biological activities. Sal A and its impurities have similar physical and chemical properties, as well as strong reducibility; therefore, they are difficult to prepare and purify. In this study, high-purity Sal A was obtained by purification of sephadex chromatography and preparative chromatography. Furthermore, HPLC-DAD tandem ECD and HPLC-DAD tandem MS methods were used for non-volatile organic impurity analysis, ICP-MS method was used for non-volatile inorganic impurities and mass balance method and quantitative nuclear magnetic resonance were employed to certify the product. The structures of Sal A and its relative impurities were validated by nuclear magnetic resonance spectroscopy and mass spectrometry, and their contents were quantified as well. Following the principles of ISO Guides 34:2009 and 35:2005, a Sal A reference material was certified, covering homogeneity studies, stability studies, characterization, and uncertainty estimations.

Betulin (BE) has exceedingly become a potential natural product, providing multiple pharmacological and biological activities, including anti-cancer, anti-viral, and anti-inflammatory benefits . Previous research indicated that the solvatomorphism of BE can easily occur through crystallization with different organic solvents. This property of BE can directly affect its extraction, isolation, and preparation process. In this study, a system of thermogravimetry (TG)–differential thermal analysis (DTA) coupled with mass spectrometry (MS) with electron ionization (EI) and photoionization (PI) capability, equipped with the skimmer-type interface (i.e., skimmer-type interfaced TG–DTA–EI/PI–MS system), as a real-time and onsite analysis technique, was employed. Then, four solvatomorphs of BE, namely, with pyridine and water (A), sec -butanol (B), n,n -dimethylformamide (DMF) (C), and isopropanol (V), were analyzed for the first time. Finally, five kinds of the main volatile gaseous species, including H 2 O, pyridine, sec -butanol, DMF, and isopropanol, were identified clearly. Furthermore, the multi-step desolvation processes of the four solvatomorphs of BE were revealed by this system for the first time. This system showed great potential for the rapid and accurate analysis of various solvatomorphs of natural products. Graphic Abstract

Betulin (BE) can be obtained from many plants, such as those belonging Betulaceae family, and pharmacological investigations showed its notable biological properties and good potential for food and pharmaceutical development. We investigated the homogeneity, stability, purity, and uncertainty of a newly certified reference material (CRM) of BE. The certified purity value for the CRM of BE was 99.56% with an extended uncertainty of 0.07% (k = 2, P = 0.95), as determined by differential scanning calorimetry (DSC). In this study, DSC was used for the first time for purity determination of BE. Given its high accuracy, precision, and reproducibility, DSC can be used as an alternative technique for purity determination of CRMs in the pharmaceutical and food industry.