Breast cancer remains a significant global health challenge, emphasizing the pressing need for innovative therapeutic approaches. Our thorough research investigates the potential of mesoporous polydopamine nanoparticles (MPDA) as a targeted treatment for breast cancer. Meticulously crafted, these nanoparticles were loaded with honokiol (HK), which is a natural product, and then coated with functionalized hyaluronic acid (HA) to boost their ability to target breast cancer cells that overexpress CD44 receptors. The deep penetrating and photothermal (PTT) composite nanosystem combined with low-dose metformin (Met) improves the efficacy of synergetic therapy against breast tumors. The designed nanosystem exhibited exceptional biocompatibility and stability, suggesting its suitability for therapeutic use. Our in vitro studies demonstrated that the nanosystem precisely targeted and penetrated breast cancer cells, resulting in significant cell death. Additionally, in vivo studies showed that the nanosystem markedly inhibited tumor growth compared to the control group. This tumor-inhibiting effect was due to the combined action of the encapsulated HK, free Met, and the photothermal effect induced by near-infrared laser irradiation. This combination potently stimulates the expression of cleaved caspase-3 and cleaved PARP proteins, ultimately triggering cell apoptosis and effectively curbing tumor proliferation. Our research not only underscores the promising potential of nanoparticles for targeted breast cancer therapy but also sets the stage for further exploration and development of novel nanomedicine-based therapeutic strategies.

In this paper, an oral liquid containing Magnolia officinalis polysaccharide was formulated and its hypoglycemic effects were investigated. An orthogonal test was conducted based on single-factor experiments to optimize the formulation guided by sensory evaluations. Its stability and safety were also assessed. The oral liquid was administered via gavage to STZ-induced diabetic mice at low (2.5 mL/kg), medium (5 mL/kg) and high (10 mL/kg) doses. Blood glucose levels were monitored weekly. After 8 weeks of treatment, the oral glucose tolerance test (OGTT) was performed and fasting insulin levels, lipid profiles, oxidative stress levels in serum and liver, and the activities of hexokinase (HK) and pyruvate kinase (PK) in the liver were measured. Results indicated that the optimal formulation contained 0.2% steviol glycosides, 0.2% ascorbic acid, a pH of 5.0, and 0.5% ginger juice, yielding a sensory evaluation score of 94 ± 0.58. The oral liquid remained stable at room temperature for 12 months and passed acute oral toxicity testing. After 8 weeks, diabetic mice exhibited a significant reduction in blood glucose levels (P < 0.01), enhanced glucose metabolism, increased fasting insulin levels, and decreased lipid levels. Additionally, antioxidant capacity improved, and HK and PK activities increased significantly in the diabetic mice. In conclusion, the Magnolia officinalis polysaccharide oral liquid demonstrated potential antidiabetic effects by promoting glucose utilization in peripheral tissues, increasing fasting insulin levels, and enhancing antioxidant capacity alongside HK and PK activities. This formulation could represent a promising hypoglycemic health product.

Honokiol (HNK) is a natural polyphenolic compound extracted from the bark and leaves of Magnolia grandiflora. It has been traditionally used as a medicinal compound to treat inflammatory diseases. HNK possesses numerous health benefits with a minimal level of toxicity. It can cross the blood-brain barrier and blood-cerebrospinal fluid, thus having significant bioavailability in the neurological tissues. HNK is a promising bioactive compound possesses neuroprotective, antimicrobial, anti-tumorigenic, anti-spasmodic, antidepressant, analgesic, and antithrombotic features . HNK can prevent the growth of several cancer types and haematological malignancies. Recent studies suggested its role in COVID-19 therapy. It binds effectively with several molecular targets, including apoptotic factors, chemokines, transcription factors, cell surface adhesion molecules, and kinases. HNK has excellent pharmacological features and a wide range of chemotherapeutic effects, and thus, researchers have increased interest in improving the therapeutic implications of HNK to the clinic as a novel agent. This review focused on the therapeutic implications of HNK, highlighting clinical and pharmacological features and the underlying mechanism of action.Communicated by Ramaswamy H. Sarma.

Chronic kidney disease (CKD) is a serious health threat worldwide. Defective mitophagy has been reported to induce mitochondrial dysfunction, which is closely associated with CKD pathogenesis. Honokiol (HKL) is a bioactive component of Magnolia officinalis that has multiple efficacies. Our study aimed to investigate the effect of HKL on a CKD rat model and explore the possible mechanisms of mitophagy mediated by Bcl-2 interacting protein 3 and BNIP3-like (NIX) (also known as the BNIP3/NIX pathway) and FUN14 domain-containing 1 (the FUNDC1 pathway) and the role of the AMP-activated protein kinase (AMPK) pathway.

A CKD rat model was established by feeding the animals dietary adenine (0.75% w/w, 3 weeks). Simultaneously, the treatment group was given HKL (5 mg/kg/day, 4 weeks) by gavage. Renal function was assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Pathological changes were analyzed by periodic acid-Schiff (PAS) and Masson's trichrome staining. Protein expression was evaluated by Western blotting and immunohistochemistry.

HKL treatment ameliorated the decline in renal function and reduced tubular lesions and interstitial fibrosis in CKD rats. Accordingly, the renal fibrosis markers Col-IV and α-SMA were decreased by HKL. Moreover, HKL suppressed the upregulation of the proapoptotic proteins Bad and Bax and Cleaved caspase-3 expression in CKD rats. Furthermore, HKL suppressed BNIP3, NIX and FUNDC1 expression, leading to the reduction of excessive mitophagy in CKD rats. Additionally, AMPK was activated by adenine, and HKL reversed this change and significantly decreased the level of activated AMPK (phosphorylated AMPK, P-AMPK).

HKL exerted a renoprotective effect on CKD rats, which was possibly associated with BNIP3/NIX and FUNDC1-mediated mitophagy and the AMPK pathway.

Alzheimer's disease (AD) constitutes one of the most complex and devastating diseases, with an extraordinarily high increase expected for the next few years. Despite the numerous efforts accomplished so far there is still no cure but just palliative treatments.

The main topic covered herein has been the development of butyrylcholinesterase (BuChE) inhibitors with the aim of increasing the levels of the neurotransmitter acetylcholine (ACh). Two main groups of compounds have been considered: multitarget and non-multitarget ligands, depending if the structural design is focused or not on other key targets and pathogenic factors of the disease. Seventeen patents regarding multitarget-directed ligands (MTDLs), twelve for not multitarget derivatives, and three for miscellaneous uses have been covered in the period 2018‒2021.

BuChE is an attractive target in the treatment of AD for many reasons. It is the most prevalent cholinesterase within more advanced stages of the disease, so drugs inhibiting it would be suitable for the treatment of mid- to severe Alzheimer's patients. Moreover, BuChE has been proved to be connected with some other key hallmarks of the disease, like amyloidogenesis; hybridization of a BuChE-targeting pharmacophore with other scaffolds designed for other therapeutic targets is quite a promising design for potential anti-Alzheimer's drugs.

Inflammation is a major factor affecting human health. Nuclear factor-kappa B (NF-κB) plays a vital role in the development of inflammation, and the promoters of most inflammatory cytokine genes have NF-κB-binding sites. Targeting NF-κB could be an exciting route for the prevention and treatment of inflammatory diseases. As important constituents of natural plants, lignans are proved to have numerous biological functions. There are growing pieces of evidence demonstrate that lignans have the potential anti-inflammatory activities. In this work, the type, structure and source of lignans and the influence on mitigating the inflammation are systematically summarized. This review focuses on the targeting NF-κB signaling pathway in the inflammatory response by different lignans and their molecular mechanisms. Lignans also regulate gut microflora and change gut microbial metabolites, which exert novel pathway to prevent NF-κB activation. Taken together, lignans target NF-κB with various mechanisms to inhibit inflammatory cytokine expressions in the inflammatory response. It will provide a scientific theoretical basis for further research on the anti-inflammatory effects of lignans and the development of functional foods.

Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic accumulation of triglycerides in the liver. Emerging evidence has demonstrated that lipophagy regulates lipid mobilization and energy homeostasis in the liver. Sirtuin 3 (SIRT3), a mitochondrial NAD⁺-dependent deacetylase, modulates the activities of several substrates involving in autophagy and energy metabolism. Honokiol (HK) is a natural lignan from the plants of Magnolia genus that exhibits potent liver protective property.

AML12 was challenged with 500 μM palmitic acid and 250 μM oleic acid mixture solution to induce lipotoxicity. C57BL/6J mice were fed with a choline-deficient high fat diet (CDHFD) to generate liver steatosis. The expression of autophagy-related and AMP-activated protein kinase (AMPK) pathway proteins was evaluated by Western blotting and immunofluorescence staining. Intracellular lipid accumulation was validated by Nile red staining. Molecular docking analysis was performed on AutoDock 4.2.

HK (5 and 10 μM) was found to attenuate lipid accumulation through promoting SIRT3-AMPK-mediated autophagy, mainly on lipid droplets. HK had hydrophobic interaction with amino acid residues (PHE294, GLU323 and VAL324) and NAD⁺. Moreover, HK improved mitochondrial function to enhance lipolysis, through decreasing the acetylated long-chain acyl-CoA dehydrogenase level. In CDHFD-fed mice, HK (2.5 and 10 mg/Kg) treatment obviously prevented lipid accumulation in the liver. And co-treatment of the AMPK inhibitor, Compound C, almost abolished the above changes.

These results suggest that HK could ameliorate lipotoxicity in hepatocytes by activating SIRT3-AMPK-lipophagy axis, which might be a potential therapeutic agent against NAFLD.