Huanglian Jiedu Decoction (HJD), one of the classic recipes for relieving toxicity and fever, is a common method for treating sepsis in China. However, the effective components of HJD have not yet been identified. This experiment was carried out to elucidate the effective components of HJD against sepsis. Thus, seven fractions from HJD were tested using a biosensor to test their affinity for lipid A. The components obtained that had high lipid A-binding fractions were further separated, and their affinities to lipid A were assessed with the aid of a biosensor. The levels of LPS in the blood were measured, and pathology experiments were conducted. The LPS levels and mRNA expression analysis of TNF-α and IL-6 of the cell supernatant and animal tissue were evaluated to investigate the molecular mechanisms. Palmatine showed the highest affinity to lipid A and was evaluated by in vitro and in vivo experiments. The results of the in vitro and in vivo experiments indicated that the levels of LPS, TNF-α and IL-6 of the palmatine group were significantly lower than those of the sepsis model group (p<0.01). The group treated with palmatine showed strong neutralizing LPS activity in vivo. The palmatine group exhibited stronger protective activity on vital organs compared to the LPS-induced animal model. This verifies that HJD is a viable treatment option for sepsis given that there are multiple components in HJD that neutralize LPS, decrease the release of IL-6 and TNF-α induced by LPS, and protect vital organs.

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Brain glioma is one of the most common and devastating intracranial malignancies with a high mortality. Chemotherapy for brain glioma is not ideal due to blood brain barrier (BBB) and multidrug resistance (MDR). The objectives of the present study were to develop a kind of RGD (Arg-Gly-Asp) tripeptide modified vinorelbine plus tetrandrine liposomes to achieve BBB transportation, MDR reversion and glioma cell targeting simultaneously. The studies were performed on glioma cells, resistant glioma cells and glioma-bearing mice. Results showed that the constructed liposomes with suitable physicochemical properties could significantly enhance the transport across BBB, obviously accumulate in glioma cells, and exhibit evident capabilities in diminishing brain glioma in mice. Action mechanism studies indicated that the enhanced anticancer efficacy could be attribute to the follows: prolonged elimination half-life (7.093 ± 1.311 h); increased AUC (28.92 ± 2.66 mg/L*h); transporting across BBB; enhanced cellular uptake; down-regulation on P-gp (0.49 ± 0.06 fold); inducing apoptosis via activating caspase 8, 9, and 3 (2.40 ± 0.22, 3.57 ± 0.29, and 4.33 ± 0.30 folds, respectively). In conclusion, the RGD modified vinorelbine plus tetrandrine liposomes may offer a promising therapeutic strategy for treatment of brain glioma.

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Allergic rhinitis (AR) is a global health problem that appears in all age groups and affects approximately 15–30% of people. Baicalin has been used for the treatment of various allergic diseases, including AR. However, the metabolic mechanisms of AR and baicalin against AR have not been systematically studied. Here, ovalbumin-sensitized AR rats were used as a model, and animal behaviour, histological analysis, enzyme-linked immunosorbent assay (ELISA) and metabolomics were used to elucidate the mechanism of baicalin for AR. The results indicated that baicalin has a protective effect on AR rats by inhibiting the release of immunoglobulin E (IgE), histamine, interleukin-1 beta (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α). In addition, ovalbumin-induced AR included modulation of arachidonic acid, leukotriene A4 (LTA4), leukotriene B4 (LTB4), α-ketoglutaric acid, phosphatidylcholine PC (20 : 4/0 : 0), PC (16 : 0/0 : 0), citric acid, fumarate, malate, 3-methylhistidine, histamine and other amino acids that are involved in arachidonic acid, histidine metabolism, the TCA cycle and amino acid metabolism. Thus, AR could be alleviated or reversed by baicalin.

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Atopic dermatitis (AD) is a common chronic skin disease driven by a T-cell-mediated immune response, with inflammation and pruritus being its main clinical manifestations. Huanglian Jiedu decoction (HLJDT), which is an ancient Chinese medicine herbal formula derived from Wai-Tai-Mi-Yao, is a potentially effective treatment for AD. We aimed to clarify the anti-inflammatory and anti-pruritus mechanisms of HLJDT in AD treatment. We performed immunohistochemistry, Western blotting, reverse transcriptase-polymerase chain reaction, Luminex-based direct multiplex immunoassay, enzyme-linked immunosorbent assays, and flow cytometry to address the abovementioned aims. HLJDT significantly reduced clinical symptoms and ear swelling in AD-like mice by inhibiting the production of cytokines [histamine, interleukin (IL)-3, IL-4, IL-5, IL-13, IL-17A, IL-31, and IL-33], substance P (SP), transient receptor potential cation channel subfamily V member 1 (TRPV-1), and gastrin-releasing peptide (GRP). Additionally, HLJDT significantly suppressed the protein expression levels and positive cell percentage of CD28, CD80, CD86, CD207, CD326, MHCII, and OX40 in the lymphoid nodes. Moreover, HLJDT significantly suppressed mRNA and protein expression of tyrosine–protein kinase (JAK1), histamine H4 receptor, and IL-4Rα, as well as the protein expression of GRP, SP, and TRPV-1 in the root ganglion. Our findings indicate that HLJDT can treat AD by regulating the antigen presentation function of dendritic cells, weakening T-lymphocyte activation, and subsequently exerting anti-inflammatory and anti-pruritus effects.

Benzothiazinones with 8-NO 2 group is a novel class of compounds with potent antitubercular activity, especially BTZ043 and PBTZ169, which covalently inhibit DprE1. 8-CN benzothiazinones is reported as another type of benzothiazinones with potent antitubercular activity. Taking this as the starting point, a series of 8-CN benzothiazinones are synthesized and evaluated for their antitubercular activity. To better understand the antitubercular activity of this series of benzothiazinones, the difference between the molecular structures of CN01 and PBTZ169 in crystal are analyzed. CN01 and PBTZ169 show completely different conformations of the piperazine ring. Density functional theory analysis (DFT) and molecular dynamics (MD) simulation are performed to provide more details to explain the different antitubercular activity. All the analysis based on crystallography, quantum chemistry, and molecular modeling lay a foundation for the subsequent structural optimization of 8-CN benzothiazinones.