Dihydroartemisinin (DHA) is a derivative of the herb Artemisia annua L. that has prominent immunomodulatory activity; however, its underlying mechanism remains elusive. Inflammatory bowel disease (IBD) is an idiopathic inflammatory condition characterized as an autoimmune disorder that includes dysfunctions in the T helper (Th)/T regulatory cell (Treg) balance, which normally plays pivotal roles in immune homeostasis. The aim of this study was to explore the potential of DHA to ameliorate IBD by restoring the Th/Treg cell balance. To this end, we established mouse models of colitis induced by oxazolone (OXA) and 2,4,6-trinitro-benzene sulfonic acid (TNBS). We then treated mice with DHA at 4, 8, or 16 mg/kg/day. DHA treatment ameliorated colitis signs and reduced lymphocyte infiltration and tissue fibrosis. Moreover, DHA decreased the numbers of Th1 and Th17 cells and Th9 and Th22 cells in TNBS- or OXA-induced colitis, respectively, and increased Tregs in both models. DHA (0.8 mg/mL) also inhibited activated CD4+ T lymphocytes, which was accompanied by apoptosis induction. Moreover, it promoted heme oxygenase-1 (HO-1) production in vitro and in vivo, concomitant with CD4+ T cell apoptosis and restoration of the Th/Treg balance, and these effects were blocked by treatment with the HO-1 inhibitor Sn-protoporphyrin IX. Overall, these results suggest that DHA is a novel and valuable candidate for IBD therapy or Th/Treg immunoregulation.

Cerebral malaria (CM) is a life-threatening neurological complication caused by Plasmodium falciparum. About 627,000 patients died of malaria in 2020. Currently, artemisinin and its derivatives are the front-line drugs used for the treatment of cerebral malaria. However, they cannot target the brain, which decreases their effectiveness. Therefore, increasing their ability to target the brain by the nano-delivery system with brain-targeted materials is of great significance for enhancing the effects of antimalarials and reducing CM mortality. This study used glucose transporter 1 (GLUT1) on the blood–brain barrier as a target for a synthesized cholesterol-undecanoic acid–glucose conjugate. The molecular dynamics simulation found that the structural fragment of glucose in the conjugate faced the outside the phospholipid bilayers, which was conducive to the recognition of brain-targeted liposomes by GLUT1. The fluorescence intensity of the brain-targeted liposomes (na-ATS/TMP@lipoBX) in the mouse brain was significantly higher than that of the non-targeted liposomes (na-ATS/TMP@lipo) in vivo (P < 0.001) after intranasal administration. The infection and recurrence rate of the mice receiving na-ATS/TMP@lipoBX treatment were significantly decreased, which had more advantages than those of other administration groups. The analysis of pharmacokinetic data showed that na-ATS/TMP@lipoBX could enter the brain in both systemic circulation and nasal-brain pathway to treat malaria. Taken together, these results in this study provide a new approach to the treatment of cerebral malaria. Graphical Abstract

Nasal administration of Traditional Chinese medicine (TCM) has a long history of applications. With the gradual maturing of technology and pharmacological advances, nasal preparations of TCM have undergone significant changes. Nasal TCM formulations are used not only for treatment of pneumonia, asthma, sinusitis and allergic rhinitis but also Alzheimer's disease and Parkinson's disease, as antidepressants and antiepileptics, and in ischemia reperfusion. However, according to the analysis of nasal preparations of TCM currently on the market, most of them were compound preparations, which were used to treat allergic rhinitis (AR), common cold, headache and other local treatments, with a small range of diseases. At the same time, the dosage forms were mainly traditional dosage forms, aerosols and sprays, but there were no new dosage forms, which can not meet the clinical needs in terms of variety number, variety diversity and disease types. In this manuscript, we reviewed the development and applications of different nasal preparations of TCM from the aspects of nasal structure, origin, factors affecting absorption and common dosage forms, pharmacodynamics, targeting of nasal delivery and safety. In the near future, we expect that more nasal preparations of Chinese medicine with independent intellectual property rights will be marketed to meet the needs of clinical disease management.

Exposure to diesel exhaust particles (DEP) increases the risk of ischemic heart disease, especially heart attacks and ischemic/thrombotic strokes. Shengmai Yin (SMY) is a traditional Chinese medicine used to treat coronary heart disease. The aim of this study was to determine the protective role of SMY and the mechanism by which SMY affects DEP-induced cardiovascular injury. This study is expected to provide the basis for the development of an adaptive signature of SMY in the prevention of atherosclerotic cardiovascular disease and premature death from global air pollution exposure. We developed animal models of myocardial ischemia and atherosclerosis (AS) in response to DEP exposure. After SMY treatment, serum lipids returned to normal. Aortic plaque area and MMP9 expression were significantly reduced and collagen fiber expression increased after SMY treatment compared to DEP exposure alone. Thus, the risk of plaque formation and vulnerability is reduced. In addition, SMY improved left ventricular structure, morphology, function, blood flow, infarct area, myocardial damage, and ROS accumulation to varying degrees in ApoE^-/- mice. These results indicate that the use of SMY is effective, to varying degrees, for the treatment of dyslipidemia, atherosclerosis, myocardial ischemia, and oxidative stress in ApoE^-/- mice. SMY has a potential protective effect in DEP-aggravated AS in people with myocardial ischemia.

Background and Purpose: Ultrafine particulate matter (UFPM) induces oxidative stress (OS) and is considered to be a risk factor of myocardial ischemia (MI). Shengmai formula (SMF) is a traditional Chinese medicine with antioxidant properties and has been used to treat cardiovascular diseases for a long time. The aim of this study was to explore the protective role of SMF and the mechanism by which it prevents myocardial injury in UFPM-exposed rats with MI.Methods: An MI rat model was established. Animals were randomly divided into five groups: sham, UFPM + MI, SMF (1.08 mg/kg⋅d) + UFPM + MI, SMF (2.16 mg/kg⋅d) + UFPM + MI, and SMF (4.32 mg/kg⋅d) + UFPM + MI. SMF or saline was administrated 7 days before UFPM instillation (100 μg/kg), followed by 24 h of ischemia. Physiological and biochemical parameters were measured, and histopathological examinations were conducted to evaluate myocardial damage. We also explored the potential mechanism of the protective role of SMF using a system pharmacology approach and an in vitro myoblast cell model with small molecule inhibitors.Results: UFPM produced myocardial injuries on myocardial infarct size; serum levels of LDH, CK-MB, and cardiac troponin; and OS responses in the rats with MI. Pretreatment with SMF significantly attenuated these damages via reversing the biomarkers. SMF also improved histopathology induced by UFPM and significantly altered the PI3K/AKT/MAPK and OS signaling pathways. The expression patterns of Cat, Gstk1, and Cyba in the UFPM model group were reversed in the SMF-treated group. In in vitro studies, SMF attenuated UFPM-induced reactive oxygen species production, mitochondrial damage, and OS responses. The PI3K/AKT/p38 MAPK/Nrf2 pathway was significantly changed in the SMF group compared with that in the UFPM group, whereas opposite results were obtained for pathway inhibition.Conclusion: These findings indicate that SMF prevents OS responses and exerts beneficial effects against myocardial injury induced by UFPM + MI in rats. Furthermore, the PI3K/AKT/p38 MAPK/Nrf2 signaling pathway might be involved in the protective effects of SMF.