Scutellaria baicalensis Georgi., a plant used in traditional Chinese medicine, has multiple biological activities, including anti-inflammatory, antiviral, antitumor, antioxidant, and antibacterial effects, and can be used to treat respiratory tract infections, pneumonia, colitis, hepatitis, and allergic diseases. The main active substances of S. baicalensis, baicalein, baicalin, wogonin, wogonoside, and oroxylin A, can act directly on immune cells such as lymphocytes, macrophages, mast cells, dendritic cells, monocytes, and neutrophils, and inhibit the production of the inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α, and other inflammatory mediators such as nitric oxide, prostaglandins, leukotrienes, and reactive oxygen species. The molecular mechanisms underlying the immunomodulatory and anti-inflammatory effects of the active compounds of S. baicalensis include downregulation of toll-like receptors, activation of the Nrf2 and PPAR signaling pathways, and inhibition of the nuclear thioredoxin system and inflammation-associated pathways such as those of MAPK, Akt, NFκB, and JAK-STAT. Given that in addition to the downregulation of cytokine production, the active constituents of S. baicalensis also have antiviral and antibacterial effects, they may be more promising candidate therapeutics for the prevention of infection-related cytokine storms than are drugs having only antimicrobial or anti-inflammatory activities.

Obesity and related metabolic syndromes have been recognized as important disease risks, in which the role of adipokines cannot be ignored. Adiponectin (ADP) is one of the key adipokines with various beneficial effects, including improving glucose and lipid metabolism, enhancing insulin sensitivity, reducing oxidative stress and inflammation, promoting ceramides degradation, and stimulating adipose tissue vascularity. Based on those, it can serve as a positive regulator in many metabolic syndromes, such as type 2 diabetes (T2D), cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), sarcopenia, neurodegenerative diseases, and certain cancers. Therefore, a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors. The modulation of ADP genes, multimerization, and secretion covers the main processes of ADP generation, providing a comprehensive orientation for the development of more appropriate therapeutic strategies. In order to have a deeper understanding of ADP, this paper will provide an all-encompassing review of ADP.

Purpose: Here, we investigated the formation and functional properties of self-assembled lecithin/chitosan nanoparticles (L/C NPs) loaded with insulin following insulin–phospholipid complex preparation, with the aim of developing a method for oral insulin delivery. Methods: Using a modified solvent-injection method, insulin-loaded L/C NPs were obtained by combining insulin–phospholipid complexes with L/C NPs. The nanoparticle size distribution was determined by dynamic light scattering, and morphologies were analyzed by cryogenic transmission electron microscopy. Fourier transform infrared spectroscopy analysis was used to disclose the molecular mechanism of prepared insulin-loaded L/C NPs. Fast ultrafiltration and a reversed-phase high-performance liquid chromatography assay were used to separate free insulin from insulin entrapped in the L/C NPs, as well as to measure the insulin-entrapment and drug-loading efficiencies. The in vitro release profile was obtained, and in vivo hypoglycemic effects were evaluated in streptozotocin-induced diabetic rats. Results: Our results indicated that insulin-containing L/C NPs had a mean size of 180 nm, an insulin-entrapment efficiency of 94%, and an insulin-loading efficiency of 4.5%. Cryogenic transmission electron microscopy observations of insulin-loaded L/C NPs revealed multilamellar structures with a hollow core, encircled by several bilayers. In vitro analysis revealed that insulin release from L/C NPs depended on the L/C ratio. Insulin-loaded L/C NPs orally administered to streptozotocin-induced diabetic rats exerted a significant hypoglycemic effect. The relative pharmacological bioavailability following oral administration of L/C NPs was 6.01%. Conclusion: With the aid of phospholipid-complexation techniques, some hydrophilic peptides, such as insulin, can be successfully entrapped into L/C NPs, which could improve oral bioavailability, time-dependent release, and therapeutic activity.

Tumor-associated macrophages (TAMs) generally display an immunosuppressive M2 phenotype and promote tumor progression and metastasis, suggesting their potential value as a target in cancer immunotherapy. Chlorogenic acid (CHA) has been identified as a potent immunomodulator that promotes the polarization of TAMs from an M2 to an M1 phenotype. However, rapid clearance in vivo and low tumor accumulation have compromised the immunotherapeutic efficacy of CHA in clinical trials. In this study, mannosylated liposomes are developed for targeted delivery of CHA to TAMs. The immunoregulatory effects of CHA, along with the overall antitumor efficacy of CHA-encapsulated mannosylated liposomes, are investigated through in vitro and in vivo experiments. The prepared CHA-encapsulated mannosylated liposomes exhibit an ideal particle size, favorable stability, and preferential accumulation in tumors via the mannose receptor-mediated TAMs-targeting effects. Further, CHA-encapsulated mannosylated liposomes inhibit G422 glioma tumor growth by efficiently promoting the polarization of the pro-tumorigenic M2 phenotype to the anti-tumorigenic M1 phenotype. Overall, these findings indicate that CHA-encapsulated mannosylated liposomes have great potential to enhance the immunotherapeutic efficacy of CHA by inducing a shift from the M2 to the M1 phenotype.

Purpose: Lecithin/chitosan nanoparticles have shown great promise in the transdermal delivery of therapeutic agents. Baicalein, a natural bioactive flavonoid, possesses multiple biological activities against dermatosis. However, its topical application is limited due to its inherently poor hydrophilicity and lipophilicity. In this study, the baicalein-phospholipid complex was prepared to enhance the lipophilicity of baicalein and then lecithin/chitosan nanoparticles loaded with the baicalein-phospholipid complex were developed to improve the transdermal retention and permeability of baicalein. Methods: Lecithin/chitosan nanoparticles were prepared by the solvent-injection method and characterized in terms of particle size distribution, zeta potential, and morphology. The in vitro release, the ex vivo and in vivo permeation studies, and safety evaluation of lecithin/chitosan nanoparticles were performed to evaluate the effectiveness in enhancing transdermal retention and permeability of baicalein. Results: The lecithin/chitosan nanoparticles obtained by the self-assembled interaction of chitosan and lecithin not only efficiently encapsulated the drug with high entrapment efficiency (84.5%) but also provided sustained release of baicalein without initial burst release. Importantly, analysis of the permeation profile ex vivo and in vivo demonstrated that lecithin/chitosan nanoparticles prolonged the retention of baicalein in the skin and efficiently penetrated the barrier of stratum corneum without displaying skin irritation. Conclusion: These results indicate the potential of drug-phospholipid complexes in enhancing the entrapment efficiency and self-assembled lecithin/chitosan nanoparticles based on phospholipid complexes in the design of a rational transdermal delivery platform to improve the efficiency of transdermal therapy by enhancing its percutaneous retention and penetration in the skin.